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HUMAN    PHYSIOLOGY 


MACMILLAN  AND  CO.,  LIMITED 

LONDON  •  BOMBAY  •  CALCUTTA 
MELBOURNE 

THE    MACMILLAN   COMPANY 

NEW   YORK  •  BOSTON  •  CHICAGO 
ATLANTA  •  SAN   FRANCISCO 

THE  MACMILLAN  CO.  OF  CANADA,   LTD. 

TORONTO 


V- 


V 


-  '     HUMAN"  "".,f 
PHYSIOLOGY 


BY 

PROFESSOR    LUIGI    LUCIANI 

DIRECTOR   OF  THE    PHYSIOLOGICAL    INSTITUTE    OF   THE   ROYAL    UNIVERSITY    OF    ROMK 

TRANSLATED    BY 

FRANCES    A.   WELBY 

EDITED    BY 

DR    M.    CAMIS 

INSTITUTE   OF   PHYSIOLOGY,    UNIVERSITY    OF    PISA 

WITH    A    PREFACE    BY 

J.    N.    LANGLEY,    F.RS. 

PROFESSOR    OF    PHYSIOLOGY    IN   THE    UNIVERSITY    OF    CAMBRIDGE 


IN  FOUR  VOLUMES 
VOL.   I.— CIRCULATION  AND  RESPIRATION 


MACMILLAN    AND    CO.,    LIMITED 

ST.    MARTIN'S    STREET,    LONDON 

1911 


PREFACE 

"  GOOD  wine  needs  no  bush,"  but  it  will  perhaps  not  be  an  in- 
fringement of  this  maxim  to  introduce,  in  a  few  words,  Professor 
Luciani's  excellent  Text-Book  of  Physiology  to  the  English-reading 
public.  The  Italian  Text-book  is  now  in  its  third  edition,  the 
final  pages  being  in  the  Press.  One  or  other  of  the  earlier  editions 
has  been  translated  into  French,  German,  and  Eussian,  and  it  is 
a  matter  for  surprise  that  we  have  had  to  wait  so  long  for  an 
English  version. 

In  the  making  of  physiological  text -books,  we  are  at  the 
parting  of  the  ways.  The  physiologists  of  the  past  generation 
were  brought  up  to  know  with  familiarity  all  that  had  been 
recently  done  in  physiological  research,  whether  in  vertebrates  or 
invertebrates,  in  animals  or  in  plants.  The  facts  were  not  so 
numerous  that  they  could  not  be  stored  in  the  memory  without 
cumbering  the  judgment,  and  Physiologists  could  in  some  sort 
be  first-hand  authorities  on  all  branches  of  the  subject.  That 
condition  has  been  gradually  passing  away,  and  it  is  hardly 
possible  for  any  one  who  is  not  of  the  old  school  to  write  an 
advanced  text-book  covering  the  whole  ground  of  Physiology. 
Thus  the  text-book  of  single  authorship  is  giving  way  to  the 
text-book  of  multiple  authorship.  The  latter,  whatever  its  merits, 
has  not  the  unity  of  view  and  the  sense  of  proportion  which 
belong  to  the  former — qualities  very  important  in  a  book  intended 
for  students. 

Professor  Luciani's  book,  whilst  describing  phenomena  with 
considerable  detail,  treats  lucidly  the  broad  principles  to  be 
deduced  from  them.  It  stands  midway  between  the  text-book 
which  confines  itself  to  summing  up  the  results  of  physiological 
investigation,  and  that  which  gives  also  a  minute  historical 
account  of  the  progress  of  investigation.  It  deals  with  the  main 


vi  PHYSIOLOGY 

outlines  of  the  history  of  each  branch  of  the  subject,  but  does  not 
allow  this  to  interfere  with  the  even  flow  of  narration. 

It  is  natural  that  writers  of  Text-books  should  make  frequent 
reference  to  the  work  that  has  been  done  by  their  own  country- 
men. Italian  work  is  less  widely  known  than  it  deserves,  and 
one  of  the  advantages  of  this  book  for  English-speaking  folk  is 
that  Italian  workers  receive  their  meed  of  notice.  It  will,  how- 
ever, be  a  shock  to  many  English  readers  to  find  that  Professor 
Luciani  allots  the  discovery  of  the  systemic  circulation  of  the 
blood  to  his  countryman,  Cesalpinus.  That  the  circulation  of  the 
blood  was  described  and  demonstrated  by  Harvey,  no  one  doubts.. 
That  there  were  a  number  of  forerunners  of  Harvey  who  under- 
stood this  or  that  important  fact  connected  with  the  circulation  is 
equally  undoubted.  In  considering  the  place  to  be  assigned  to 
each  of  those  who  helped  to  solve  the  problem,  two  separate 
questions  arise.  First,  How  far  are  the  facts  and  views  original 
and  not  obtained  from  unacknowledged  sources  ?  and  secondly, 
What  was  the  exact  degree  of  understanding  of  the  subject 
possessed  by  each  writer  ?  It  may  seem  that  the  former  question 
only  would  be  difficult  to  solve.  In  fact,  the  difficulty  of  the 
latter  is  no  less,  or  at  any  rate  differences  of  opinion  with  regard 
to  it  have  not  been  less  ardent ;  and  so  we  find  that  whilst  most, 
authorities  regard  Cesalpinus  as  having  but  imperfectly  compre- 
hended the  systemic  Circulation,  and  to  have  seen  it  "  darkly 
through  Galenical  glasses,"  some,  as  Professor  Luciani,  consider 
that  his  comprehension  was  whole  and  without  flaw. 

Finally,  it  may  be  noted  that  the  Editor,  Dr.  Camis,  has 
added  at  the  end  of  each  chapter  a  selected  list  of  English-written 
Monographs  and  Papers,  and  thus  has  put  the  student  who 
knows  no  other  language  than  English  in  the  way  of  obtaining 
a  fuller  knowledge  of  any  branch  of  Physiology  in  which  he  may 
be  interested. 

J.  N.  LANGLEY. 

CAMBRIDGE,  Jaw.  1911. 


TRANSLATOR'S   NOTE 

I  BEG  to  offer  my  sincere  thanks  to  Dr.  Aders-Plimmer 
for  his  kind  help  in  the  translation  of  the  chemical 
section  of  this  volume :  and  to  Mr.  W.  L.  Symes  for 
assistance  in  many  other  technical  difficulties. 

FRANCES  A.  WELBY. 

LONDON,  October  1910. 


vii 


>• 


CONTENTS 


PACK 


INTRODUCTION   .  1 

1.  Threefold  division  of  biological  science.  2.  Special  objects  of 
physiology.  3.  Materialism,  nee-vitalism,  Ostwald's  energetic  monism, 
Mach's  psychical  monism,  pragmatic  pluralism.  4.  Physiology  of 
the  cell ;  general  and  comparative  physiology  ;  human  physiology. 
Bibliography. 


CHAPTER   I 

LIVING  MATTER  :  ITS  CHEMICAL  AND  PHYSICAL  BASIS          .  .11 

1.  The  cell-theory.  2.  Morphology  of  the  cell.  3.  Structure  of 
protoplasm.  4.  Structure  of  nucleus.  5.  Chemical  elements  of  the 
cell.  6.  Protein  basis  of  living  matter.  7.  Classification  of  proteins. 
8.  Chemical  constitution  of  proteins.  9.  Enzymes  or  ferments.  10. 
Classification.  11.  Other  nitrogenous  organic  substances,  fats,  carbo- 
hydrates or  saccharides,  inorganic  substances.  12.  Chemical  structure 
of  living  matter.  Bibliography. 


CHAPTER    II 

LIVING  MATTER  :  ITS  FUNDAMENTAL  PROPERTIES     .  .       42 

1.  Vital  metabolism,  and  phenomena  of  nutrition  and  repro- 
duction. 2.  Vital  metabolism  and  phenomena  of  excitability  and 
sensibility.  3.  Laws  of  stability  and  variability  of  living  species. 
Critical  examination  of  Theory  of  Evolution  ;  Darwinism,  and  Neo- 
Lamarckism.  4.  Evolutionary  theories  of  Nageli,  Weismann,  De  Vries. 
5.  Distinctive  characters  of  plants  and  animals :  (a}  Doctrine  of 
Linnaeus  ;  (b)  doctrine  of  Cuvier  ;  (c)  doctrine  of  J.  R.  Mayer,  Dumas, 
Liebig.  6.  Different  forms  of  plant  and  animal  metabolism  :  (a)  Nitri- 
fying bacteria  ;  (&)  green  plants  ;  (c)  a-chlorophyllous  plants  ;  (d) 
herbivorous  and  carnivorous  plants.  Bibliography. 

ix 


x  PHYSIOLOGY 

CHAPTER  III 

PAGE 

LIVING  MATTER  :  CONDITIONS  BY  WHICH  IT  is  DETERMINED  .       64 

1.  Nutrition  the  necessary  external  condition  of  vital  metabolism. 
Phenomena  of  inanition.  2.  Importance  of  water.  Latent  life  and 
anabiosis.  3.  Importance  of  oxygen.  Aerobic  and  anaerobic  life.  4. 
External  temperature  indispensable  to  life.  5.  Total  pressure  of  air 
and  water,  and  partial  pressure  of  oxygen  and  carbonic  acid.  6.  Ex- 
ternal stimuli.  7.  Chemical  stimuli.  Chemotaxis.  8.  Mechanical 
stimuli.  Barotaxis.  9.  Thermal  stimuli :  thermotaxis.  10.  Photic 
stimuli.  Phototaxis  and  Heliotaxis.  11.  Electrical  stimuli.  Galvano- 
taxis.  12.  The  various  biological  zones  of  ocean  life  (Plankton}.  13. 
Internal  conditions  and  stimuli  of  metabolism.  Theory  of  automatism. 
14.  Hypotheses  to  explain  the  intimate  mechanism  of  living  matter. 
Bibliography. 

CHAPTER   IV 

THE  BLOOD:  FORMED  CONSTITUENTS  .  .  .  .91 

1.  Arrangement  of  human  physiology,  aild  classification  of  functions. 
2.  Importance  of  the  blood  as  centre  of  the  vegetative  system  and  agent 
of  general  metabolism.  3.  Historical  development  of  haematology. 
4.  General  physico-chemical  characters  of  the  blood.  5.  Estimation 
of  total  quantity.  6.  Physical  and  morphological  characters  of  erythro- 
cytes,  and  estimation  of  their  relative  quantity.  7.  Chemical  compo- 
sition. Properties  of  haemoglobin  and  its  derivatives.  8.  Character, 
composition,  and  physiological  properties  of  leucocytes.  9.  Blood 
platelets,  and  elementary  granulation  of  the  blood.  Bibliography. 


CHAPTER   V 

THE  BLOOD  :  PLASMA  .  .  .  .  .  .123 

1.  Different  methods  for  separation  of  blood  plasma  from  corpuscles. 
2.  Histogenic  substances  or  proteins  of  plasma  :  fibrinogen,  serum 
globulin,  serum  albumin,  sero  -  mucoid.  3.  Nitrogenous  histolytic 
products  of  plasma.  4.  Fatty  substances.  Carbohydrates  and  their 
derivatives.  5.  Inorganic  substances.  Blood  gases.  6.  Theory  of 
Coagulation :  (a)  Conditions  of  blood  coagulation  ;  (b)  disintegration 
of  corpuscles  as  cause  of  coagulation  ;  (c)  fibrinogen  as  fibrin  generator  ; 
(d)  analogies  between  blood  coagulation  and  curdling  of  milk  ;  (e)  im- 
portance of  time  in  coagulation  ;  (/)  thrombin  and  nucleins  as  coagu- 
lating substances  ;  (g)  histone  and  cytoglobulin  as  anti-coagulating 
substances.  7.  Osmotic  pressure,  molecular  concentration,  electrical 
conductivity  and  viscosity  of  blood  and  serum.  8.  Functions  of  the 
blood  :  (a)  effects  of  bleeding  ;  (b)  effects  of  transfusion  of  homo-  and 
heterogeneous  blood  ;  (c)  bactericidal  and  immunising  properties  of 
blood  and  serum.  Bibliography. 


CONTENTS  xi 

CHAPTER   VI 

PACK 

THE  CIRCULATION  OF  THE  BLOOD  :  DISCOVERY          .  .  .157 

1.  Physiological  necessity  for  the  circulation  of  the  blood.  Schema 
of  cardio-vascular  system.  2.  Theory  of  Galen.  3.  Discovery  of  the 
lesser  circulation.  Question  of  the  priority  of  Columbus,  Servetus, 
and  Vesalius.  4.  Discovery  of  the  general  circulation  by  Cesalpinus. 
5.  Completion  of  the  work  by  Harvey.  6.  Discovery  of  the  lymph 
circulation  by  Eustachius,  Aselli,  Pecquet,  Rudbeck,  Bartholin.  7. 
Discovery  of  the  capillary  system,  and  direct  observation  of  the  circu- 
lation by  Malpighi.  8.  Microscopic  observations  of  the  phenomena  of 
circulation.  Spallanzani,  Poiseuille,  R.  Wagner,  etc.  9.  Discovery  of 
diapedesis  of  blood -corpuscles  and  migration  of  leucocytes  :  Waller, 
Addison,  Recklinghausen,  Cohnheim.  Bibliography. 

CHAPTER   VII 

MECHANICS  OF  THE  HEART  .  .  .  .  .180 

1.  Description  of  cardiac  cycle  or  revolution.  2.  Changes  of  external 
form,  of  the  internal  cavity,  of  the  position  and  volume  of  the  heart  in 
the  different  phases  of  its  activity.  3.  Mechanism  of  semilunar  valves. 
4.  Mechanism  of  auriculo-ventricular  valves.  5.  Theory  of  so-called 
heart -sounds.  6.  Variations  of  pressure  within  the  auricles  and 
ventricles  during  the  cardiac  cycle.  7.  The  diastolic  aspiration ; 
various  explanatory  hypotheses.  8.  Cardiac  plethysmograms  ;  theory 
of  active  diastole.  9.  Cardiograms  ;  theory  of  heart-beats  or  impulses. 
10.  Other  mechanical  effects  of  cardiac  activity.  11.  Work  done  by 
the  heart.  Bibliography. 

CHAPTER   VIII 

THE  BLOOD-STREAM  :  MOVEMENT  IN  THE  VESSELS  .  .  .232 

1.  Fundamental  laws  of  hydrodynamics  for  passage  of  fluid  through 
rigid  tubes.  2.  Application  of  these  laws  to  haemodynamics.  3.  Me- 
chanical effects  of  elasticity  of  vessel-walls  and  intermittence  of  flow  of 
blood  from  heart ;  laws  of  wave  motion.  4.  Method  of  measuring  and 
automatically  registering  variations  in  blood  pressure.  5.  Principal 
results  obtained.  6.  Methods  of  measuring  velocity  of  circulation  ; 
experimental  results.  7.  Sphygmography  and  sphygmograms  repre- 
senting pulsatory  oscillations  in  pressure.  8.  Comparison  of  cardio- 
grams and  sphygmograms  registered  simultaneously,  indicating  duration 
of  the  principal  phases  of  cardiac  cycle  in  man.  9.  Comparison  of  several 
sphygmograms  registered  simultaneously  from  arteries  at  different 
distances  from  the  heart,  indicating  rate  of  transmission  of  primary 
and  of  dicrotic  wave.  10.  Tachymetr-y  and  tachygrams  representing 
pulsatory  variations  in  current  velocity.  11.  Pletliysmography  and 


xii  PHYSIOLOGY 

PAfi  K 

plethysmogranis  representing  pulsatory  oscillations  in  the  volume  of  the 
arteries.  12.  Schema  of  mechanical  conditions  of  the  circulation  in  the 
three  great  vascular  systems  ;  determination  of  duration  of  the  entire 
circulation.  Bibliography. 


CHAPTER   IX 

PHYSIOLOGY  OF  CARDIAC  MUSCLE  AND  NERVES  .285 

1.  Intrinsic  processes  by  which  cardiac  rhythm  is  determined  and 
regulated.  2.  Extrinsic  chemical  conditions  of  cardiac  activity.  3. 
Effects  of  ligation  and  section  on  different  parts  of  the  heart.  4. 
Automatic  or  reflex  activity  of  heart.  5.  Myogenic  or  neurogenic 
origin  of  cardiac  rhythm.  6.  Evidence  for  these  conflicting  theories. 

7.  Special  mode  in  which  cardiac  muscle  reacts  to  external  stimuli. 

8.  Regulation   of  cardiac   rhythm   by  nervous  system  ;   inhibitory  or 
diastolic   nerves.     9.  Accelerator    or    systolic    nerves.     10.  Theory   of 
anabolic   action   of  diastolic   nerves   and   katabolic  action  of  systolic 
nerves.     11.  Afferent  nerves  of  heart  or  other  parts  of  the  body,  which 
influence    cardiac    rhythm.       12.   Nerve    centres   for    cardiac  .  nerves ; 
their  tonic  excitability,  and  theory  of  regulation   of  cardiac  rhythm. 
Bibliography. 

CHAPTER   X 

PHYSIOLOGY  OF  VASCULAR  MUSCLE  AND  NERVES      .  .  .341 

1.  Discovery  of  vasomotor  nerves.  2.  Vascular  tone  and  its 
rhythmic  and  a-rhythmical  variations,  as  depending  essentially  upon 
the  automatic  and  reflex  excitability  of  the  smooth  muscle  cells.  3. 
Theory  of  vaso-constrictor  nerves.  4.  Theory  of  vaso-dilator  nerves. 
5.  Vascular  reflexes.  6.  Bulbar  vaso-constrictor  centre.  7.  Spinal 
and  cerebral  centres  for  vaso-constrictor  nerves.  8.  Centres  for  vaso- 
dilator nerves.  Bibliography. 

CHAPTER   XI 

CHEMISTRY  AND  PHYSICS  OF  EESPIRATORY  EXCHANGES         .  .     369 

1.  Early  notions  of  the  importance  of  respiration  (Aristotle,  Galen, 
Leonardo  da  Vinci,  van  Helmont,  Boyle,  Hook,  Fracassati,  Lower, 
Mayow).  2.  Modern  doctrines  (Black,  Bergmann,  Priestley,  Lavoisier). 
3.  Theory  of  gas  exchanges  in  the  lungs  and  tissues  (Lagrange  and 
Spallanzani,  W.  Edwards).  4.  Extraction  of  gases  from  the  blood 
(Magnus,  L.  Meyer,  Hoppe  -  Seyler,  Ludwig,  Pfliiger).  5.  Varying 
content  of  arterial,  venous,  and  asphyxiated  blood.  6.  State  of  the 
oxygen  in  the  blood.  7.  State  of  the  carbonic  acid  in  the  blood.  8. 
Tension  of  gases  in  venous  and  arterial  blood  and  in  inspired  and  ex- 
pired air  ;  theory  of  pulmonary  gas  exchange  by  diffusion  and  by 
secretory  processes.  9.  Theory  of  gas  exchanges  in  the  tissues.  10. 
The  respiratory  quotient  and  its  variations.  Bibliography. 


CONTENTS 


Xlll 


CHAPTER   XII 

MECHANICS  OF  RESPIRATION  .  .  . 

1.  Historical.  2.  Glandular  structure  of  the  lungs.  3.  Conditions 
of  the  lungs  and  other  viscera  within  the  thorax  ;  passive  movements 
due  to  variations  in  the  negative  thoracic  pressure.  4.  The  thoracic 
cavity  ;  changes  of  form  and  dimensions  with  inspiratory  and  expiratory 
movements.  5.  Muscular  mechanism  of  inspiratory  and  expiratory 
movements.  6.  Normal  and  forced  respiration.  7.  Accessory  or  con- 
comitant respiratory  movements.  8.  Ventilation  or  renewal  of  pul- 
monary air  (spirometry),  and  respiratory  pressure  in  the  air -passages 
(pneumatometry).  9.  Respiratory  displacement  of  the  lungs,  and 
acoustic  phenomena  of  percussion  and  auscultation.  10.  Respiratory 
variations  of  iiitrathoracic  and  intra-abdominal  pressure.  11.  Respira- 
tory variations  of  pressure  in  the  vena  cava.  12.  Respiratory  variations 
of  aortic  pressure.  13.  Effect  of  respiratory  mechanics  on  the  circula- 
tion of  the  blood.  14.  Special  forms  of  respiratory  movements. 
Bibliography. 

CHAPTER    XIII 

THE  NERVOUS  CONTROL  OF  RESPIRATORY  RHYTHM 

1.  Motor  nerves  to  respiratory  muscles  and  smooth  muscle  cells  of 
bronchi.  2.  Bulbar  respiratory  centres  and  their  localisation.  3.  Spinal 
respiratory  centres.  4.  Cerebral  respiratory  centres.  5.  Each  of  these 
centres  results  from  the  association  of  an  inspiratory  and  an  expiratory 
centre,  which  function  rhythmically  and  alternately.  6.  Automatic 
regulation  of  normal  respiratory  rhythm,  by  afferent  pulmonary  fibres 
of  vagus.  7.  Influence  exerted  on  respiratory  rhythm  via  the  cerebral 
tracts  and  sensory  nerves  in  general.  8.  Phenomena  consequent  on 
the  separation  of  the  bulb  from  the  brain  and  spinal  cord.  9.  Dyspnoea 
and  its  different  forms.  10.  Eupnoea  or  normal  quiet  respiration. 

11.  Experimental  apnoea  from  artificial  respiration  with  the  bellows. 

12.  Foetal  apnoea,   and  the  analogous  forms  of  experimental  apnoea 
that  can  be  produced  in  the  adult.     13.  Voluntary,  as  compared  with 
experimental  apnoea.     14.  Apnoea  produced  by  continuous  ventilation 
in   birds.     15.   Periodic   respiration,    or   Cheyne  -  Stokes    phenomenon. 
16.   Physiological  theory  of  respiratory  rhythm.     Bibliography. 


PAGE 

402 


440 


CHAPTER   XIV 

THE   LYMPH,  AND    INTERCHANGES  BETWEEN  THE    BLOOD    AND    THE 

TISSUES         ...  .     505 

1.  Structure  of  lymphatic  vascular  system,  lymph  spaces,  sinuses 
and  cavities.  2.  Origin  ;  physical,  morphological  and  chemical  charac- 
teristics ;  qualitative  and  quantitative  variations  of  lymph.  3.  Lymph- 
atic circulation,  and  the  various  mechanical  factors  by  which  it  is 


xiv  PHYSIOLOGY 

determined.  4.  Formation  of  lymph  from  the  blood  capillaries,  and 
the  so-called  lymphagogues.  5.  Secretory  theory  of  Heidenhain,  and 
transudation  theory  of  Cohnheim.  6.  Formation  and  modification  of 
lymph  by  the  tissues.  7.  Lymphoid  tissue,  follicles  and  lymphatic 
glands.  8.  Bone  marrow.  9.  The  thymus.  10.  The  spleen. 
Bibliography. 


INDEX  OF  SUBJECTS     .  .561 

INDEX  OF  AUTHORS  573 


INTRODUCTION 


1.  Threefold  division  of  biological  science.  2.  Special  objects  of  physiology. 
3.  Materialism,  neo- vitalism,  Ostvvald's  energetic  monism,  Mach's  psychical  monism, 
pragmatic  pluralism.  4.  Physiology  of  the  cell ;  general  and  comparative 
physiology  ;  human  physiology.  Bibliography. 

THE  remarkable  development  of  Physiology  during  the  nine- 
teenth century  justifies  us  in  regarding  it  as  one  of  the  most 
modern .  sciences ;  yet  its  origin  is  very  ancient,  and  may  be 
traced  back  to  the  first  flashes  of  philosophic  thought.  Through- 
out the  classical  world,  however,  with  few  exceptions,  the  term 
Physiology  (according  to  its  etymological  signification)  connotes 
the  philosophic  study  of  Nature  in  general,  i.e.  it  includes  the 
phenomena,  not  merely  of  living  nature,  but  of  inanimate  nature 
as  well. 

During  the  Middle  Ages,  again,  until  the  Eenaissance,  the 
Science  of  Life  is  confounded  with  Philosophy,  with  Natural 
History,  with  Medicine  in  general,  and  in  particular  with  Anatomy. 

In  the  second  half  of  the  eighteenth  century  the  immense 
progress  made  in  the  vast  field  of  Natural  History  (so-called) 
involved  a  corresponding  division  of  labour.  Intimate  relations 
obtain  between  mineralogy,  geology,  and  physical  geography. 
These  are  complementary  and  reciprocal  subjects,  which  are  all 
included  among  the  inorganic  natural  sciences.  Most  intimate, 
too,  are  the  links  connecting  botany  and  zoology :  "  Between 
plants  and  animals,"  as  was  happily  said  by  Buffon,  "  there  are 
more  common  properties  than  real  differences."  Between  dead  and 
living  nature,  however,  the  gap  is  far  wider,  the  differences  more 
essential,  and  the  study  of  the  one  may  be  undertaken  independent 
of  the  other. 

At  the  commencement  of  the  last  century  two  eminent  natural- 
ists, Lamarck  in  France,  and  Treviranus  in  Germany,  created  the 
word  Biology,  and  applied  it  in  the  first  instance  to  designate 
the  complex  of  closely  related  sciences  which  covers  the  phenomena 
observed  in  living  beings  in  general,  i.e.  in  plants,  animals,  and 
man. 

VOL.  II  B 


2  PHYSIOLOGY 

But  if  Biology  is  to  include  the  complete  study  of  life  in  all 
its  manifestations,  it  represents  a  field  too  vast  to  admit  of 
comprehension  by  any  single  mind  in  all  its  details.  Hence  the 
necessity  arises  for  a  further  division  of  labour. 

I.  If  at  any  given  moment  of  its  existence  we  set  out  to 
consider  the  mode  of  life  and  action  of  any  living  being,  we  can  at 
once  distinguish  the  morphological  characteristics,  depending  ©n 
anatomical  and  histological  structure,  from  the  functional  or 
physiological  features,  which  are  dependent  on  its  cytological, 
physical,  and  chemical  constitution.  If  in  living  beings  we 
consider  the  development,  the  perpetual  becoming,  in  other  words 
the  morphological  and  physiological  changes  they  undergo  from 
beginning  to  end  of  their  existence,  we  have  the  story  of 
Evolution,  which  enables  us  to  a  certain  point,  both  for  the  indi- 
vidual and  the  species,  to  follow  the  different  phases  of  development 
as  these  fulfil  themselves  according  to  the  great  laws  of  heredity 
and  variation. 

The  complete  study  of  life,  to  which  the  term  Biology  has  thus 
been  applied,  is  appropriately  divided  into  three  branches : — 

(a)  Morphology,  which  covers  the  forms  of  living  beings,  i.e. 
the  cellular  elements  from  which  the  tissues  are  built'  up,  the 
connections  of  the  tissues  whence,,  the  organs  develop,  the 
structure  of  the  organs  and  systems. 

(ft)  Physiology,  which  covers  the  functions  or  activities  of 
living  beings,  and  the  various  cytological,  physical,  and  chemical 
factors  from  which  these  arise :  in  other  words,  the  storage  and 
dispersal  of  the  energies  of  which  organisms  are  the  seat,  and  the 
phenomena  or  external  manifestations  by  which  they  are  revealed 
to  us. 

(c)  Biogenesis,  i.e.  the  story  of  evolution,  morphological  as  well 
as  functional,  whether  ontogenetic,  for  the  individual,  or  phylo- 
genetic,  for  the  race. 

The  intimate  connections  of  these  three  great  branches  of 
biological  science  are  obvious.  Since  organic  form  is  the  necessary 
matrix  of  function,  the  study  of  Physiology  perforce  includes  that 
of  Morphology,  or  Anatomy — as  the  latter  is  commonly  but  loosely 
termed.  These  two  branches  are  really  offshoots  of  the  same 
trunk,  inasmuch  as  they  constituted  in  bygone  times  a  single 
science  professed  by  a  single  teacher,  when  the  (vastly  pre- 
dominating) study  of  the  morphological  signs  of  life  was  identified 
in  various  ways  with  that  of  its  physiological  properties.  But  as 
the  study  of  form  has  methods  of  research  and  problems  which  are 
separate  and  quite  distinct  from  those  relating  to  function, 
anatomy  has  gradually  detached  itself  from  physiology,  pursuing 
its  own  independent  development.  The  History  of  Evolution  or 
Biogenesis,  again,  which  covers  a  vast  field  of  researches  in  em- 
bryology, comparative  anatomy,  and  palaeontology,  is  evidently 


INTRODUCTION 

an  offshoot  from  the  common  trunk  of  Morphology  and 
In  so  far  as  it  studies  the  development  of  forms  it  is  intimately 
related  to  morphology ;  inasmuch  as  it  investigates  the  develop- 
ment of  functions  it  is  united  by  the  closest  bonds  with  physiology. 

This  threefold  development  of  biology  rests  on  no  profound 
scientific  postulate,  but  merely  arises  from  the  convenience  of  a 
division  of  labour,  whether  in  fulfilment  of  a  didactic  necessity  or  in 
order  more  rapidly  to  approach  the  ideal  of  a  comprehensive  know- 
ledge of  living  phenomena.  We  may  reasonably  anticipate  that 
in  proportion  as  the  task  assigned  to  each  department  approaches  its 
completion,  and  the  corresponding  methods  of  investigation  are 
exhausted,  the  relations  will  become  more  intimate,  and  the 
intercourse  between  the  workers  in  the  three  several  fields  more 
frequent,  till  finally  the  great  Science  of  Life,  completed  by  all  the 
achievements  of  morphology,  physiology,  psychology,  and  natural 
science,  is  reconstituted  in  its  initial  unity,  as  was  predicted  by 
Lazzaro  Spallanzani  and  Johannes  Miiller. 

Of  late  years  the  special  province  of  Physiology  has  become 
so  vast  that  a  considerable  area  of  it  is  now  set  apart  under  the 
name  of  Chemical  Physiology,  and  it  may  seem  as  though  we 
were  still  very  far  from  the  synthetic  reconstitution  of  Biology 
as  a  unitary  and  well-organised  science — an  ideal  image  of  the 
living  organism.  Owing,  however,  to  the  aforesaid  division  of 
labour,  or  to  the  undeniable  exhaustion  of  certain  superannuated 
methods  in  other  directions,  General  or  Comparative  Physiology, 
an  important  department  which  was  too  much  neglected  in  the 
past,  has  been  developed  and  perfected ;  this  comprises  the  collec- 
tive study  of  elementary  organisms,  in  which  Cytology  and  Proto- 
Morphology  present  to  morphologists  and  physiologists  a  common 
field  of  research. 

II.  In  the  study  of  the  living  organism,  the  physiologist  sets 
himself  three  main  tasks :  to  define,  to  localise,  and  to  interpret  the 
phenomena  of  life.  He  aims  at 

(a)  Definition  of  vital  phenomena :  by  describing  them  exactly, 
forming,  if  possible,  a  graphic  image  that  shall  be  accurate,  not 
merely  in  its  outlines,  but  also  in  its  minutest  details. 

(&)  Localisation  of  the  different  vital  phenomena  in  the  several 
substrata :  by  determining  the  specific  energies  developed  by  the 
various  elements,  tissues,  organs,  and  systems  of  which  the  body  is 
composed. 

(c)  Explanation  or  interpretation  of  vital  phenomena:  by  in- 
quiry into  their  genesis  and  inner  mechanism,  investigation  of 
the  external  or  internal  conditions  on  which  they  depend,  deter- 
mination of  the  qualitative  and  quantitative  changes  they  undergo 
in  the  play  of  the  said  conditions. 

These  three  tasks  represent  three  different  grades  of  physiological 
science.  The  first  is  purely  descriptive;  the  second,  descriptive 


4  PHYSIOLOGY 

and  experimental;  the  third,  descriptive,  experimental,  and 
speculative.  For  the  first,  direct  or  indirect  observation,  i.e.  the 
exact  perception  of  vital  phenomena,  suffices — whether  by  the 
normal  use  of  the  senses  only  or  by  the  help  of  instruments 
designed  to  reinforce  them.  For  the  second,  observation  is  not 
enough,  experiment  also  is  required,  i.e.  premeditated  observation, 
in  which  the  external  and  internal  conditions  of  the  living 
phenomena  can  be  varied.  In  the  third,  besides  observation  and 
experiment,  an  energetic  criticism  is  imperative,  i.e.  the  logical 
elaboration  by  the  physiologist  of  the  collected  analytical  data,  in 
order  to  interpret  and  synthetise  them.  This,  in  the  majority 
of  cases,  resolves  itself  into  the  arrangement  of  vital  facts  in 
order  of  co-existence  and  succession,  or  of  co-ordination  and  sub- 
ordination. 

In  the  first  grade  of  physiological  science  we  have  an  accumu- 
lation of  loose  facts,  more  or  less  unorganised,  but  adapted  to  call 
up  a  picture  of  the  various  and  manifold  energies  of  which  the 
living  organism  is  the  seat.  In  the  second,  we  arrive  at  an 
ordering  and  systematisation  of  the  said  energies,  which  enables 
us  more  or  less  clearly  to  conceive  what  Galen  called  the  "  usu& 
partium,"  i.e.  the  topography  of  the  vital  functions.  The  third 
aims  at  harmonising  the  same  energies,  an  order,  by  our  knowledge 
of  the  influences  exerted  by  each  element  or  organ  upon  the 
other  elements  or  organs  of  which  the  body  consists,  to  form  an 
idea  as  to  how  that  individual  unity  is  built  up,  which  is  revealed 
to  us  subjectively  as  the  ego,  objectively  as  the  complete  harmony 
of  functions  that  characterises  the  state  of  perfect  health. 

The  first  and  second'  grades  of  physiological  science  have  a 
positive,  immanent  value,  which  time  can  only  develop  and  per- 
fect, while  the  third  has  seldom  more  than  a  hypothetical  value, 
which  is  for  the  most  part  temporary,  and  therefore  varies  with 
time.  It  follows  that  facts,  if  well  observed,  and  experimental 
data  well  harvested,  are  and  will  for  ever  be  true  in  the  progress 
of  science,  while  the  interpretation  of  facts,  and  their  logical 
order,  may  vary  greatly,  and  even  alter  fundamentally,  with  the 
advent  of  new  data  or  new  discoveries. 

III.  In  the  interpretation  of  vital  phenomena,  the  physiologist 
seeks  to  apply  the  known  laws  of  physics  and  chemistry,  starting 
from  the  obvious  position  that  organised  bodies  cannot  lie  beyond 
-the  scope  of  the  laws  of  Nature.  The  interpretation  of  these  laws 
is  entirely  based  on  the  atomistic  hypothesis  of  matter,  with  its 
corollary  that  the  indivisible  elements  of  which  matter  is  com- 
posed are  in  themselves  indestructible  and  invariable  in  their 
fundamental  properties,  having,  i.e.,  the  same  specific  weight,  the 
same  valency  or  saturation  capacity,  the  same  affinity.  The 
energy  of  which  the  atoms  are  the  seat  may  be  potential  or 
kinetic.  The  former  is  transformed  into  the  latter,  and  vice  versa,. 


INTKODUCTION  5 

either  without  change  of  the  atomic  groups  (physical  phenomena), 
or  with  changes  in  the  same  (chemical  phenomena). 

These  great  empirical  laws  of  the  Conservation  of  Matter 
(Lavoisier,  1789)  and  the  Conservation  of  Energy  (J.  E.  Mayer, 
1842;  Helmholtz,  1847)  dominate  living  as  well  as  non-living 
Nature.  A  living  being  objectively  considered  may  be  conceived 
as  a  machine  transforming  the  matter  and  energy  it  derives  from 
the  external  world.  As  a  physico-chemical  science  of  life, 
physiology  will  have  fulfilled  its  task  when  it  is  able  to  provide 
an  adequate  mechanical  representation  of  the  inner  processes  which 
underlie  the  vital  somatic  phenomena,  that  is,  when  it  succeeds 
in  giving  a  satisfactory  explanation  of  these  phenomena,  and  in 
describing  the  processes  on  which  they  depend  as  links  in  the 
causal  chain  of  the  grand  Procession  of  Nature. 

The  immense  value  of  atomic  and  molecular  mechanics, 
considered  as  -the  basis  of  vital  phenomena  (i.e.  Physiological 
Materialism  in  the  modern  and  scientific  sense),  is  best  appreciated 
in  reviewing  the  vast  and  rapid  progress  made  by  physiology, 
since  it  has  applied  the  positive  methods  of  physics  and  chemistry 
to  the  study  of  life,  and  has  abjured  the  vain  abstract  speculations 
used  and  abused  at  the  beginning  of  the  last  century  by  the 
so-called  "  natural  philosophers." 

At  the  same  time  no  sincere  worker  in  the  positive  or  scientific 
direction  can  deny  that  the  specifically  vital  somatic  phenomena, 
i.e.  those  by  which  living  beings  are  differentiated  from  inorganic 
bodies,  are  inexplicable  by  the  known  laws  of  chemistry  and 
physics,  and  that  the  psychical  phenomena  (of  sensibility  and 
consciousness),  which  for  each  individual  constitute  the  culminating 
point  of  life,  are  altogether  remote  from  any  mechanical  explana- 
tion :  they  cannot  in  any  way  be  regarded  as  necessary  links 
in  the  chain  of  cause  and  effect  in  the  natural  processes  of  Nature. 

It  is  probable  that  not  a  few  of  the  still  unexplained  physio- 
logical phenomena  will  become  intelligible  in  the  further  progress 
of  physics  and  chemistry ;  but  even  so,  such  phenomena  as  are 
specifically  vital,  and  psychical  phenomena,  will  remain  refractory 
to  any  mechanical  explanation. 

The  dynamic  finality  proper  to  living  beings  (which  is  essenti- 
ally distinct  from  the  static  finality  of  the  cognate  parts  of  a 
machine  created  by  human  industry) ;  the  capacity  for  repro- 
duction, reintegration,  adaptation  ;  the  innate  tendency  to  evolve, 
to  progress,  to  become  perfect,  with  relative  independence  of 
environmental  conditions, — these  and  other  specific  phenomena  of 
living  beings  must,  to  all  who  are  emancipated  from  theoretical 
dogmatism,  appear  irreducible  to  a  simple  play  of  physical  and 
chemical  energies,  irreconcilable  with  the  iron  necessity  of 
mechanical  laws.  This  is  the  position  assumed  by  Neo-vitalisin, 
which  starts  from  this  affirmation  and  transcends  the  earlier 


6  PHYSIOLOGY 

Vitalism,  inasmuch  as  it  recognises  the  experimental  method  as  the 
exclusive  means  of  scientific  progress. 

When,  on  the  other  hand,  we  consider  psychical  phenomena 
(sensibility  and  consciousness),  the  impossibility  of  reducing  these 
to  physical  and  chemical  processes  becomes  even  more  apparent. 

Ostwald  (1902)  has  recently  attempted  to  formulate  a  unitary 
conception  of  the  world  by  excluding  the  materialistic  postulates 
of  natural  science,  i.e.  by  eliminating  the  chemical  concept  of  the 
atoms  and  substituting  the  physical  concept  of  energy,  psychical 
processes  being  regarded  as  special  manifestations  of  energy.  This 
Energetic  Monism  of  Osfcwald  is,  however,  illusory.  It  is  a  new 
and  degenerate  presentation  of  the  old  Idealistic  Monism  of  Hegel, 
in  which  the  word  energy  is  substituted  for  the  empty  word  "  idea," 
although  equally  devoid  of  definite  content.  In  what,  then,  does 
the  essential  difference  between  the  various  forms  of  physical  and 
that  of  the  supposed  psychical  energy  consist  ?  In  that  the  former 
are  perceptible  solely  by  the  mediation  of  the  senses,  the  latter  by 
introspection  alone — the  first  being  objective,  the  second  subjective 
phenomena  ?  It  is,  however,  precisely  in  this  antithesis  that  the 
vulgar  dualistic  doctrine  of  the  corporeal  as  distinct  from  the 
spiritual  world  arises.  This  theory, -which  was  adumbrated  by 
primitive  man  from  his  observations  of  death  (as  appears  from 
ethnological  and  prehistoric  studies),  became,  in  the  course  of 
centuries,  deeply  embedded  in  the  mind  of  the  whole  civilised 
world,  resisting  like  a  granite  block  the  most  potent  and  repeated 
attempts  of  scientific  and  philosophical  critics  to  dislodge  it.  Du 
Bois-lleymond  says  in  this  connection:  "It  is  fundamentally 
impossible  to  explain  by  any  mechanical  means  why  the  note 
of  a  Konig's  tuning-fork  gives  me  pleasure,  while  contact  with 
red-hot  iron  gives  me  pain  "  (1872). 

A  more  profound  (but  in  our  opinion  no  less  illusory) 
attempt  to  arrive  at  a  monistic  conception  is  that  put  for- 
ward by  Mach  in  his  well-known  Analysis  of  the  Sensations, 
and  the  Relations  of  the  Physical  and  Psychical  (3rd  ed.,  1902). 
According  to  Mach  the  dualism  between  body  and  soul  exists  in 
appearance  only,  and  results  from  a  superficial  observation  of 
reality.  More  profound  reflection  shows  that  the  ultimate 
elements  of  reality  are  nothing  but  sensations.  The  entire 
corporeal  world,  organic  or  inorganic,  is  for  us  nothing  but  an 
aggregate  of  sensations ;  the  whole  of  our  thought  is  similarly 
constituted  of  a  more  or  less  complex  combination  of  sensations. 
Hence  there  is  no  reason  to  postulate  an  essential  difference,  still 
less  an  antagonism,  between  the  physical  fact  and  the  psychical 
fact ;  the  one  like  the  other,  in  last  resort,  results  from  homo- 
geneous elements.  The  disparities  are  in  appearance  only,  and 
depend  upon  the  different  construction  of  the  aggregates,  while 
the  elements  of  these  are  quantitatively  identical. 


INTRODUCTION  7 

It  is  obvious  that  if  this  mode  of  philosophising  (which  recalls 
the  mystical  phenomenalism  of  Berkeley  with  his  "  esse  est 
percipi")  is  to  give  us  a  monistic  representation  free  from  all 
hypothesis,  not  only  the  chemical  concept  of  atoms,  but  also  the 
physical  concept  of  energy  must  be  given  up,  the  psychical  concept 
of  sensations  alone  being  retained  as  the  ultimate  homogeneous 
and  irreducible  element  of  reality.  To  be  strictly  logical,  we 
must  cancel  the  entire  doctrine  of  physics  and  chemistry,  as  based 
upon  mere  hypothesis,  and  throw  ourselves  into  the  arms  of  pure 
psychology,  which  alone  enjoys  the  privilege  of  having  for  its 
content  the  aggregates  of  the  homogeneous  elements  of  reality ! 
But  how  can  we  understand  the  manifold  qualitative  differences  in 
these  aggregates,  if  once  we  admit  them  to  arise  from  qualitatively 
identical  elements  ?  How  conceive  of  physical  facts,  and  what  in 
common  parlance  is  called  the  "  external  world,"  as  a  complex  of 
sensations,  if  we  make  an  abstraction  of  the  internal  world,  by 
means  of  which  alone  these  are  to  arise  as  such  in  consciousness  ? 
How  can  the  physiologist  imagine  a  sensation  as  divorced  from 
the  law  of  causality  and  independent  of  the  stimulus  that  excites 
it  ?  Is  it  not  absurd  to  admit  an  essential  identity  between  the 
esse  and  the  nosse,  the  esse  and  the  posse  ?  How  are  we  to 
reconcile  Mach's  view,  according  to  which  the  psychical  fact  is 
presented  as  something  less  real  than  —  almost  (as  it  were)  a 
shadow  of — the  physical  fact,  with  his  general  doctrine,  according 
to  which  the  physical  and  the  psychical  are  said  to  be  identical 
in  their  nature  ? 

If  we  inquire  from  the  followers  of  Mach  what  pragmatic 
value  can  attach  to  Psychical  Monism  (or  Phenomenalism,  or 
Empirical  Criticism,  as  it  is  termed  by  others)  they  admit  that 
it  is  nil  when  we  are  concerned  with  scientific  work  in  the 
various  fields  of  research.  "  Here  all  remains  as  before  "  (writes 
Max  Verworn,  1905),  "  methods,  symbols,  facts,  relations  are  all 
untouched.  Scientific  work  pursues  its  course  unchecked."  This 
is  equivalent  to  an  admission  that  both  the  atomistic  and  the 
energetic  hypotheses  (which  constitute  Materialism),  and  the 
hypothesis  of  vital  or  psychical  force  (which  constitutes  Neo- 
vitalism),  must  continue  to  function  as  indispensable  instruments, 
as  poles  or  presumptions  necessary  to  future  discoveries  and  to 
the  progress  of  science  in  general.  In  order  to  build  up  science 
we  are  constrained  to  descend  from  the  rarefied  regions  of  abstrac- 
tion, and  to  live  in  the  world  of  concrete  facts,  grappling  with 
the  vital  processes  in  their  varied  and  complex  phenomenology, 
whether  mechanical  or  psychical ;  in  other  words,  Monism  must 
be  completed  by  Pluralism,  according  to  our  immediate  experi- 
ence. 

Each  new  physiological  experiment,  each  new  scientific 
conquest,  appears  as  a  more  or  less  important  integration  of  the 


8  PHYSIOLOGY 

science  of  the  living ;  it  always  signifies  a  process  that  either 
tends  to  apply  the  mechanical  explanation  to  a  supposed  vital 
phenomenon,  or  brings  out  the  essentially  vital  character  of  a 
supposed  physico-chemical  phenomenon. 

The  evolutionary  process  of  physiological  science  has  always 
been  in  the  past,  and  will  always  be  in  the  future,  a  continuous 
and  fruitful  struggle  between  the  two  opposite  tendencies  of 
Materialism  and  Vitalism.  It  is  a  mistake  to  suppose  that  either 
the  one  or  the  other  will  ever  win  the  final  victory.  Both  are 
one-sided  ;  both  reflect  one  face  only  of  reality.  Life,  in  its  more 
highly  evolved  forms,  results  from  their  interpenetration  and 
fusion.  Seen  from  without,  it  is  })ody  :  felt  from  within,  it  is 
soul :  this  is  the  great  mystery  that  Art  for  ever  celebrates — ra 
mystery  Science,  with  every  possible  and  conceivable  progress 
in  physics  and  chemistry,  with  all  the  experimental  methods  that 
it  may  or  might  employ,  will  never  be  in  a  position  to  solve. 

IV.  As  the  physico-chemical  science  of  living  beings,  Physiology 
includes  the  comparative  study  of  the  vital  phenomena  of  plants, 
animals,  and  man. 

Some  vital  phenomena  are  common  to  all  living  beings, 
without  distinction  of  species,  genera,  classes,  or  kingdoms.  These 
are  fundamental  phenomena,  that  is,  they  are  the  simplest  and 
most  elementary  in  life.  Their  material  substratum  -is  the  Cell,  i.e. 
the  simplest  morphological  unit,  which  Briicke  calls  the  elementary 
organism,  whether  living  its  independent  life,  or  living  in 
association  with  other  cells  to  form  cell  aggregates  or  complex 
organisms. 

The  physiology  of  the  cell  lies  at  the  foundation  of  all 
physiology,  because  the  functions  of  the  tissues,  organs,  and 
systems  can  ultimately  be  reduced  to  the  vital  activity  of  the 
various  cells  from  which  they  evolve.  Plant  physiology,  as  well 
as  animal  and  human  physiology,  derive  the  fundamental  data 
relating  to  elementary  functions  from  the  physiology  of  the  cell, 
and  employ  it  as  a  basis  in  their  study  of  the  complex  and  special 
functions  of  the  several  tissues,  organs,  and  systems. 

The  science  of  physiology  calls  for  a  different  arrange- 
ment and  development,  and  may  assume  a  different  aspect  and 
even  content,  according  as  it  is  approached  from  a  scientific, 
a  philosophical,  or  a  medical  and  practical  standpoint.  From 
the  first  two  it  assumes  the  form  and  content  of  general  and 
comparative  physiology,  which  is  the  necessary  complement  of 
general  and  comparative  morphology;  both  are  directed  to  the 
high  aim  of  illustrating,  tabulating,  and  developing  the  grand 
doctrine  of  Evolution  or  Descent,  which  from  Darwin  onwards  has 
been  undergoing  constant  transformation  and  integration.  From 
the  third  it  assumes  the  form  and  content  of  human  physiology, 
taking  Man  as  the  goal  of  its  investigations;  it  harvests  the 


INTRODUCTION  9 

experimental  data  directly  obtained  from  the  higher  animals ;  it 
utilises  the  data  derived  from  pathological  observations,  which  not 
seldom  have  a  value  comparable  with  that  of  experiments  on 
animals ;  and  it  dwells  with  special  insistence  on  such  theories  as 
have  received  or  may  receive  an  application  to  hygiene  or  preven- 
tive medicine,  and  to  clinical  or  curative  medicine. 

Such  essentially  practical  objects  are  dealt  with  in  this  Text- 
book, which  aims  at  bringing  the  latest  advances  in  science 
within  reach  of  all  who  are  working  at  medicine  and  at  physical 
and  psychological  science, — and  seeks  at  the  same  time  to  equip 
the  younger  students,  as  adequately  as  may  be,  with  that  knowledge 
of  Physiology  which  lies  at  the  foundation  of  all  scientific  culture 
and  education. 

BIBLIOGRAPHY 

The  following  list  comprises  only  such  classical  Treatises  on  Physiology  as 
will  be  of  most  use  to  students  in  following  the  historical  development  of  any 
given  physiological  question  : — 

CLAUDIUS  GALENUS.     De  usu  partium  corporis  humani.     Lib.  xvii. 

A  DE  HALLER.     Elementa  physiologiae  corporis  humani,    1757-66.     Auctarium, 

1780. 
JOH.  MULLER.     Handbuch  d.  Physiologic  des  Menschen.     4th  ed.     Coblenz,  1844. 

(French  translation  with  Littre's  note.     Paris,  1857.) 
H.  MILNE-EDWARDS.     Lecons  sur  la  physiologic  et  1'anatomie  comparee.     Paris, 

1857-86. 

F.  A.  LONGET.     Traite  de  physiologie.     Leipzig,  1879-81. 
L.  HERMANN.     Handbuch  d.  Physiologie.     Leipzig,  1879-81. 
E.  A.  SCHAFER.     Text-book  of  Physiology.     Edinburgh  and  London,  1898-1900. 
W.  NAGEL.     Handbuch  d.   Physiologie  des  Menschen.     Brunswick  (in  course  of 

publication). 
H.    BEAUNIS   and   V.   ADUCCO.     Elementi    di   fisiologia   umana,  comprendenti   i 

principii  di  fisiologia  comparata  e  di  fisiologia  generale.     Turin  (in  course  of 

publication). 


CHAPTEE   I 

LIVING   MATTER:   ITS    CHEMICAL   AND    PHYSICAL    BASIS 

CONTENTS.— 1.  The  cell-theory.  2.  Morphology  of  the  cell.  3.  Structure  of 
protoplasm.  4.  Structure  of  nucleus.  5.  Chemical  elements  of  the  cell.  6.  Protein 
basis  of  living  matter.  7.  Classification  of  proteins.  8.  Chemical  constitution  of 
proteins.  9.  Enzymes  or  ferments.  10.  Classification.  11.  Other  nitrogenous 
organic  substances,  fats,  carbohydrates  or  saccharides,  inorganic  substances. 
12.  Chemical  structure  of  living  matter.  Bibliography. 

IN  Nature  no  phenomena  can  be  independent  of  a  material  sub- 
stratum :  all  are  the  external  manifestation  of  the  energies  im- 
manent in  matter.  Every  vital  phenomenon  that  comes  under  the 
observation  of  the  physiologist  is  intimately  connected  with  the 
living  organism,  and  is  the  expression  of  internal  causes,  i.e.  of  the 
different  forms  of  energy  inherent  within  that  organism. 

Whoever,  then,  approaches  the  threshold  of  Physiology  in  order 
to  study  the  Manifestations  of  Life,  will  feel  it  essential  to  have 
some  knowledge  of  the  material  substratum  out  of  which  the 
living  phenomena  have  been  evolved. 

I.  Both  in  plants  and  animals  the  material  substratum  of  vital 
phenomena,  the  physical  basis  of  life,  consists  of  a  substance  of 
highly  complicated  structure  and  constitution,  soft  or  gelatinous 
in  consistency,  to  which  Hugo  Mohl  (1846)  gave  the  name  of 
protoplasm.  In  living  beings  this  does  not  appear  as  a  simple 
mass,  without  form  or  boundaries ;  but  it  is  divided  into  minute 
particles,  or  separate  entities,  known  as  cells.  Each  cell  comes 
from  a  pre-existing  cell,  just  as  every  living  being  comes  from  the 
ovum,  which  is  the  primitive  cell.  The  so-called  Protista,  which 
are  the  most  primitive  form  of  life  (and  probably  constitute  the 
common  stock  whence  plants  and  animals  have  developed)  are 
throughout  their  whole  life  represented  by  a  single  cell,  which 
assumes  various  forms  and  dimensions.  In  the  Metazoa,  on  the 
contrary,  the  primitive  cell,  or  ovum,  gives  rise  to  other  similar 
cells,  and  these  to  other  cells  in  turn,  which  are  gradually  differ- 
entiated, transformed,  and  adapted  to  the  several  physiological 
offices  which  they  serve. 

11 


12  PHYSIOLOGY  CHAP. 

In  the  Protista  each  cell  is  a  distinct  and  independent  physio- 
logical individual ;  in  the  Metazoa  each  cell  or  cell-derivative  is 
still  a  distinct  individual,  but  it  is  no  longer  independent,  since 
the  life  of  each  is  more  or  less  bound  up  with  the  life  of  the  others 
with  which  it  is  associated.  The  individuality  of  the  social  aggre- 
gate, or  that  of  the  organism  as  a  whole,  is  but  an  individuality 
of  a  higher  order,  i.e.  it  is  the  sum  of  the  life  of  each  elementary 
organism.  This  is  essentially  the  Cell  Theory,  formulated  by 
Schleiden  (1838)  and  Schwann  (1839),  reinforced  and  developed 
by  Virchow  (1855),  and  fully  confirmed  by  later  observers. 

Yet  among  living  physiologists  there  are  not  wanting  some 
who  believe  that  we  must  recognise  a  more  radical  difference 
between  the  independent  unicellular  organisms  and  the  cells  of 
which  complex  organisms  are  built  up.  The  latter,  it  is  said,  since 
they  are  incapable  of  living  apart  from  the  body  of  which  they 
form  a  part,  do  not  constitute  a  real  individual,  BO  that  the  name 
of  elementary  organisms  given  them  by  Briicke  is  inappropriate. 
Since  the  several  physiological  functions  essential  to  life  are  very 
unequally  divided  among  the  various  cells  of  which  the  complex 
organism  consists,  they  must  each  represent  a  physiologically 
simpler  unit,  and  are  not  therefore  comparable  with  the  cells  that 
constitute  a  true  individual,  and  which  are  capable '  of  living 
independent  of  other  cells  (E.  Schenk  and  J.  Loeb). 

There  is  a  certain  amount  of  truth  in  this  observation,  but  the 
conclusions  deduced  from  it,  i.e.  the  negation  of  the  cell  theory, 
are  somewhat  far-fetched.  In  the  first  place  it  should  be  noted 
that  incapacity  to  live  independent  of  other  cells  cannot  be  predi- 
cated of  all  the  cells  of  which  multicellular  organisms  are  composed ; 
it  rises  gradually  with  the  zoological  scale  (cf.  Chap.  III.  12).  It 
should  further  be  observed  that  the  life  of  every  organism  is 
invariably  conditioned  by  its  special  environment,  so  that  it  perishes 
when  transported  into  other  media  too  unlike  those  in  which  it 
normally  exists.  In  unicellular  organisms  the  environment  is 
represented  by  the  sum  of  the  nutritive  materials  and  the  stimuli 
which  reach  them  from  the  external  world ;  in  the  cells  of  which 
multicellular  organisms  are  built  up  the  medium  is  represented 
by  the  sum  of  the  nutritive  matters  and  the  stimuli  which  reach 
them,  either  from  the  external  world  or  from  the  other  cells  with 
which  they  live  in  association.  Lastly,  in  the  first  as  in  the 
'second  kind  of  cell  a  different  grade  or  trend  of  development  may 
be  observed  for  each  of  their  vital  functions. 

For  the  rest,  the  cell  theory,  which  affirms  a  certain  functional 
autonomy  of  the  morphological  elements  of  which  the  organism  as 
a  whole  consists,  is  founded  on  a  synthesis  of  experimental  facts 
that  can  be  easily  verified, 

(a)  The  survival  for  a  certain  time  of  parts  detached  from  a 
living  organism. 


LIVING  MATTEK 


13 


(&)  The  non-synchronous  death  of  the  several  tissues  or  organs 
of  which  the  organism  is  composed. 

(c)  The  localisation  of  the  effects  of  toxins  and  pathogenic 
causes. 

(d)  The  possibility  of  transplanting  and  grafting  tissues  and 
organs. 

(e)  The  possibility  of  multiplying  not  only  plants,  but  also 
many  of  the  lower  multicellular  animals,  for  instance  the  fresh- 
water Hydra  by  merotomy,  or  division  into  segments. 

II.  The  organisation  of  a  perfect  cell,  capable  of  living  and 
reproducing  itself,  requires  not  merely  a  simple  lump  of  proto- 
plasm, as  was  originally  maintained 
by  M.  Schultze  (1863)  and  subse- 
quently by  E.  Haeckel  (1870),  but 
the  interior  of  the  protoplasmic  mass 
must  also  contain  a  nucleus,  a  con- 
stituent already  described  by  previous 
observers  as  an  essential  part  of 
elementary  organisms.  The  later 
work  of  Gruber  (1888)  on  Ehizopoda 
and  of  Biitschli  (1890)  on  Bacteria, 
has  shown  that  these  also  consist  of 
two  characteristically  differentiated 
parts,  corresponding  to  the  cell  proto- 
plasm or  cytoplasm,  and  the  nucleus 
of  the  perfect  cell.  The  membrane 
which  envelops  the  protoplasm  cannot 
be  regarded  as  an  essential  part  of 
the  cell,  because  while  rarely  absent 
in  plants,  it  is  almost  always  lacking 
in  the  animal  cell.  The  centrosome 
described  by  van  Beneden  and  Boveri 
(1887),  and  considered  by  them  to 
be  the  third  element  of  the  cell, 
appears  from  the  more  recent  work  of  Hertwig  (1891)  and 
Brauer  (1893)  to  be  part  of  the  nuclear  substance,  which  is 
generally  extruded  into  the  cytoplasm  during  the  activity  of  the 
nucleus,  to  incite  germination  and  cell  division.  The  morpho- 
logical concept  of  the  cell  is  accordingly  very  simple  :  it  is  funda- 
mentally a  lump  of  protoplasm  which  includes  a  more  or  less 
distinct  nucleus. 

The  importance  of  the  nucleus  to  the  life  of  the  cytoplasm  can 
be  demonstrated  experimentally,  as  also  the  importance  of  the 
cytoplasm  to  the  life  of  the  nucleus. 

The  first  experiment  consists  in  bisecting  a  unicellular  animal, 
e.g.  an  Amoeba  (Fig.  1),  in  such  a  way  that  one  half  contains  the 
nucleus  and  the  other  is  deprived  of  it :  and  then  observing  under 


FIG.  1. — Amoeba  protcus.  (Hertwig.)  M, 
nucleus ;  vc,  contractile  vacuole ;  ?, 
ingesta ;  en,  granular  endoplasm  or 
granuloplasm ;  ec,  hyaline  ectoplasm 
or  hyaloplasm. 


14 


PHYSIOLOGY 


CHAP. 


the  microscope  the  behaviour  and  final  modifications  of  the  half 
provided  with,  and  that  destitute  of  nucleus.  When  the  operation 
is  effected  with  as  little  injury  as  possible,  the  edges  of  the  cut 
soon  unite  again,  and  each  half  of  the  amoeba  contracts,  assuming 
a  globular  form.  After  a  few  seconds  each  of  these  two  globules 
begins  to  move,  changing  its  shape  and  creeping  along,  as  is  the 
normal  habit  of  intact  amoebae.  Later  on,  however,  a  difference 
between  the  two  halves  is  perceptible,  and  while  the  new  nucleated 
amoeba  continues  to  live  and  grow,  and  behaves  as  a  normal 
individual,  the  half  without  a  nucleus  slackens  its  movements, 
takes  no  more  food,  retracts  its  pseudopodia,  and,  according  to  the 
best  results  obtained  by  Hofer,  dies  in  ten  or  twelve  days.  This 

proves  the  vital  importance 
••     '  of  the  nucleus. 

The  second  experiment, 
designed  to  show  the  vital 
importance  of  the  cyto- 
plasm, was  carried  out  by 
Verworn  on  a  species  of 
Radiolaria ;  Thalassicolla 
(Fig.  2).  In  this  animal  it 
is  possible  to  shell  out  the 
nucleus,  separating  it  from 
the  ray-shaped  mass  of  the 
protoplasm,  and  to  observe 
the  effects  of  isolation. 
Even  when  the  operation 
succeeds  without  any  per- 

12.  —  Thalassicollti    nudeata.      (Verworn.)     From  CCptlble    nuclear    lesion,   the 

without,    inwards:    radiating    corona    of   pseudo  -  «„«!«„«       inpvitnhlv 

podia;  gelatinous  layer;   layer  of  vacuoles;  pig.  nuCJCUS      mevitaDly 

mented  sheath  to  central  capsule  ;  central  capsule  without    showing    any 
with  nucleus.                       •  t          6          «7 

oi  regeneration. 

A  third  experiment  consists  in  bisecting  a  unicellular  organism, 
in  such  a  way  that  each  half  contains  a  portion  of  the  nucleus  and 
a  portion  of  protoplasm.  This  succeeds  readily  in  a  trumpet- 
shaped  Infusorian  called  Stentor,  in  which  both  protoplasm  and 
nucleus  are  elongated  (Fig.  3).  When  bisected  each  half 
continues  to  live,  and  regenerates  gradually  into  a  perfect  Stentor, 
although  of  smaller  dimensions.  This  fact  cannot  be  adduced 
against  the  theory  which  considers  the  cell  as  the  lowest  step  in 
the  scale  of  living  individuality,  because  each  half  of  the  divided 
Stentor  has  the  value  of  a  cell  containing  the  two  essential 
constituents,  nucleus  and  cytoplasm.  It  merely  shows  that  the 
living  matter  in  the  said  cellular  constituents  may  vary  quanti- 
tatively to  a  considerable  extent,  without  forfeiting  the  conditions 
necessary  to  the  constitution  of  a  complete  individual. 

Just  as  a  half-cell  may  live  and  regenerate  into  a  complete 


FIG 


LIVING  MATTEK 


15 


cell,  so,  on  the  other  hand,  a  number  of  cells  fusing  their  protoplasm 
into  a  single  mass  may 
compose  a  single  multi- 
nuclear  cellular  in- 
dividual (Fig.  4).  Multi- 
nuclear  cells  are  fairly 
common,  whether  as  a 
living  species  or  as  the 
complex  elements  of 
higher  organisms.  They 
represent  transitional 
forms  between  the 
simple  niononuclear  cell 
and  a  tissue,  which  is 
an  aggregate  of  similar 
but  individually  dis- 
tinct cells.  In  some  of 
the  lower  creatures, 
known  as  Myxomycetes, 
the  multinuclear  proto- 
plasmic mass  assumes 
externally  the  aspect  of 


FIG.    3.  — 


Stentor  Roesdii.  (Verworn.)  1,  Complete  in- 
dividual, trumpet -shaped,  showing  in  the  body -axis  a 
very  elongated  nucleus  of  lighter  appearance.  When 
bisected  at  A,  each  segment  regenerates  into  a  smaller, 
complete  individual,  the  upper  half  being  represented  by 
2,  the  lower  by  3. 


a   network  which   may 

cover  an  area  of  several 

decimetres    (plasmo- 

dium).    This  reproduces 

by  spores,  and  from  each  spore  there  develops  an  amoeboid  cell  of 

distinct  outlines.  Eventually 
the  outlines  of  the  cells  dis- 
appear, and  they  resume  the 
form  of  a  reticulated  plasmo- 
dium  (Strasburger).  This 
fusion  of  many  cells  into  a 
simple  multinuclear  proto- 
plasmic mass  is  termed  a 
syncytium  (Fig.  5). 

The  external  form  of  the 
cell  may  vary  greatly  both 
in  organisms  which  consist  of 
a  single  morphological  ele- 
ment, and  in  multicellular 
organisms.  A  primary  dis- 
tinction must  be  made  be- 

Fio.    4.— Kvdorina    degans.      (Verworn.)     Complex  fWPPT1  ppll-    nf    variahlp     flnrl 

individual  (colony)  resulting  from  fusion  of  a  SWeen  C                     VRriaDlC,    ana 

number  of  flagellated  individuals  into  a  common  those  of     fixed     form.         The 

globular  mass  of  gelatinous  substance.  ,      .  , 

former  are  termed  amoeboid, 
because  they  change  their  shape  like  the  Amoebae  (Fig.  1),  which 


16 


PHYSIOLOGY 


CHAP. 


are  little  naked  protoplasmic  bodies  with  no  enclosing  membrane, 
having  often  a  distinct  nucleus.  These  put  out  in  all  directions 
projections  of  their  body- substance,  or  pseudopodia,  which  are 
continually  changing  in  shape.  The  majority  of  cells,  however, 
possess  a  constant  form,  whether  the  protoplasm  be  enclosed  in 


Fio.  5. — Chondrioderma  di/orme, — life  phases.  (Stras burger.)  o,  dry  spore  ;  b,  turgid  spore  ;  c,  d, 
dehiscence  of  spore-membrane  and  escape  of  cell-contents  ;  e,f,  g,  transformation  of  primitive- 
spore  into  pi ri ton n  and  flagellate  zoospore ;  h,  zonspore  passing  into  state  of  myxamoeba ; 
i,  i,  young  myxamoebae  ;  k,  k,  adult  myxamoebae  ;  7,  adherent  myxamoebae  ready  to  fuse  ;  ?n, 
young  plasmodium  ;  n,  portion  of  adult  reticulated  plasmodium. 

a  membrane  or  not.    Many  permanent  forms  repeat  the  temporary 
shapes  assumed  by  the  amoeboid  cells. 

The  size  of  the  cells,  again,  varies  greatly,  though  they  are 
almost  always  of  microscopic  dimensions.  The  smallest  Bacteria 
measure  only  a  few  thousandths  of  a  millimetre,  while  the  largest 
Amoebae  exceed  a  tenth  of  a  millimetre.  The  cells  of  the  higher 
organisms,  Man  included,  are  rarely  more  than  eight  hundredths 


LIVING  MATTER 


17 


-.-jtfTZ. 


~r 


of  a  millimetre  in  their  largest  diameter.  Muscle  fibres,  indeed, 
both  plain  and  striated,  may  measure  more  than  a  decimetre,  and 
the  nerve  processes  of  the  ganglion  cells  more  than  a  metre.  Still 
the  amount  of  living  matter  contained  within  a  cell  is  always, 
comparatively  speaking,  very  small.  In  a  bird's  egg,  which  is  a 
single  colossal  cell,  the  active,  living  protoplasm  consists  only  of  one 
very  delicate  layer,  the  whole  of  the  rest  being  inactive  yolk,  which 
is  destined  to  feed  the  germ  during  its  embryonic  development. 

III.  Both  in  animal  and  in  plant  cells,  protoplasm  has  the 
same  common  properties :  it  appears  as  a  semi-fluid,  almost 
always  colourless  substance,  with  no  apparent  morphological 
structure,  although  it  contains  a  variable  quantity  of  small 
punctiform  gran- 
ules ;  it  is  readily 
permeable  by  water, 
which  swells  it  up 
without  dissolving 

it ;  impenetrable  as  ^mc  •---'•^^^^^m^m^^m^^^-n 
a  rule  to  colouring 
matters  during  life, 
it  stains  readily  after 
death.  When  at 
rest  it  has  an  alka- 
line reaction,  which 
may  become  neutral 
or  even  acid  during 
activity.  The  hya- 
line, non-granulated 

protoplasm  Often  FK;I  o. —Epithelial  cell  from  intestine  of  insect  larva.     (Carnoy.) 

forms    in     the  Cell    a  mc>    ce^   membrane ;   pc,  cell   protoplasm   in   form   of  net- 

"  j  work    with     granulations;    mil,     nuclear    membrane;    pn, 

more     Or     leSS  dense  nuclear  protoplasm  with  a-chromatic,  reticulated  substance ; 

externallayer,known 

as  ectoplasm  or  hyaloplasm,  to  distinguish  it  from  the  internal 
granular  portion  that  surrounds  the  nucleus,  the  so-called  endo- 
plasm  or  granuloplasm  (Fig.  1). 

Under  the  high  power  of  the  microscope,  this  apparently 
homogeneous  protoplasm  shows  a  very  complicated  structure. 
Remak  (1844)  and  M.  Schultze  (1871)  affirmed  that  there  was  a 
fine  fibrillar  structure  in  the  protoplasm  of  the  ganglion  cells  of 
the  nervous  system,  a  theory  subsequently  extended  to  epithelial, 
glandular,  and  other  cells.  Fromman  (1865)  and  Heitzmann 
(1873)  modified  this  statement,  and  assumed  a  finely  reticulated 
structure,  in  which  the  granules  would  be  the  nodal  points  of  the 
protoplasmic  network.  Carnoy  (1883),  while  admitting  the  theory 
of  a  reticulum,  affirmed  that  the  granulation  represented  not  the 
network  but  the  fluid  contained  in  its  meshes,  to  which  he  gave 
the  name  of  enchylema  (Fig.  6).  Finally,  Butschli  (1892)  showed 

VOL.  I  C 


18 


PHYSIOLOGY 


CHAP. 


that  the  reticulum  existed  in  appearance  only,  and  was  merely  the 
optical  expression  of  the  finest  vesicles  in  close  apposition.  Pro- 
toplasm thus  consists  of  a  foam-like  ground-substance,  constructed 


FKJ-  7> Alveolar  structure  of  protoplasm.    (Biitschli.)    a,  Delicate  foam  of  alveolar  structure 

obtained  by  prolonged  whipping  of  olive  oil  and  cane-sugar;  b,  alveolar  structure  of  intra- 
capsular  protoplasm  from  ThalassicoUa  nudeata,  as  in  Fig.  2. 

in  the  form  of  delicate  polyhedric  vesicles  or  alveoli,  closely  pressed 
together.  The  protoplasmic  granules  lie  in  greater  or  less  num- 
bers at  the  corners  of  the  foam-bubbles,  never  in  the  liquid  of  the 
alveoli  themselves  (Fig.  7). 

Even  under  the  low  power,  apparently 
homogeneous  prptoplasm  not  infrequently 
exhibits  drops  of  fluid,  or  vacuoles,  as  they 
are  somewhat  infelicitousjy  termed.  Such 
accidental  vacuoles  must  be  distinguished 
from  the  permanent  ones,  which  are  so 
numerous  and  conspicuous  in  certain  plant 
cells  as  to  give  a  spongy  appearance  to  the 
protoplasm  (Fig.  8).  Rhythmically  pulsating 
vacuoles  may  sometimes  be  observed ;  these 
empty  themselves  on  contracting,  and  refill 
with  fluid  on  dilating.  This  is  especially  the 
case  in  certain  kinds  of  Amoebae,  and  is  very 
y  I  l\  frequent  among  the  ciliated  Infusoria.  In 

these  cases  the  vacuoles  function  as  a  centre 
of  circulation  for  the  protoplasmic  fluid. 

Besides  the  vacuoles,  there  are  in  vege- 
table  protoplasm   granules   of    chlorophyll, 
FIO.  s. -ceii  from  staminai  starch,  and  aleuron  :  in  animal  protoplasm, 
hair  of  Trad  esc  an  tia  fat  globules,  accumulations  of  glycogen,  and 

virgimca.       (Strasburger.)  =>    .  '  ,      .      ...      „  =>  J       &     . ' 

The  nucleus  is  surrounded  granules  known  as  "  vitellm.       The  chloro- 
1  phyll   corpuscles  are  of  capital  importance 


to  the  plant  cell,  since  the  most  characteristic 
part  of  its  vital  processes  depends  on  them ;  viz.  the  reduction  of 
carbonic  acid,  and  fixation  of  carbon.     The  granules  of  starch, 
aleuron,  fat,  glycogen,  and  vitellin  are  nutritive  materials,  products' 
of  protoplasmic  activity,  stored  up  within  the  cell. 


i  LIVING  MATTEE     .  19 

Lastly,  it  should  be  noted  that  the  unicellular  animals  which 
have  no  membranes,  such  as  amoebae,  leucocytes,  infusoria,  and 
other  cells,  often  contain  food-stuffs  or  other  solid  bodies  which 
they  have  ingested,  e.g.  diatoms,  small  algae,  bacteria,  etc. 
(Metschnikoff),  which  are  gradually  digested,  and  appear  as  solid 
inclusions  in  the  protoplasm  (see  Fig.  1). 

IV.  Many  of  the  peculiarities  which  we  have  noted  in  the 
constitution  or  structure  of  the  cytoplasm  are  characteristic  of  the 
nucleus  also.     This  is  usually  a  vesicular  body,  surrounded  by  a 
membrane ;  at  other  times  it  may  assume  various  forms,  and  may 
lose  the  enveloping  membrane  which  divides  it  from  the  cytoplasm. 

Under  a  high  magnification  Biitschli  detected  an  alveolar 
structure  similar  to  that  of  the  cytoplasm,  which  presents  the 
appearance  of  a  reticulum.  The  vesicles  contain  the  nuclear  fluid  ; 
the  substance  which  forms  them  is  termed  a-chromatic,  since  it 
does  not  stain  with  carmine,  haematoxylin,  or  other  dyes.  Another 
substance,  peculiar  to  the  nucleus,  which  does  stain  with  dyes,  and 
is  termed  chromatic,  can  also  be  distinguished.  This  appears  in 
the  form  of  small  granules  or  filaments,  threads  diffused  at  the 
nodal  points  of  the  a-chromatic  substance,  or  collected  in  a  heap 
or  kind  of  central  skein  (see  Fig.  6). 

V.  Chemical  analysis  of  animal  and  vegetable  organisms  has 
shown    that    the    elements   which    enter    most    constantly   and 
abundantly  into  the  composition  of  the  cell  are  : — 

Name.  Symbol.          Atomic  Weight. 

Carbon C  12 -00 

Nitrogen N  14-04 

Sulphur S  32-07 

Hydrogen      .         .  H  TOO 

Oxygen O  16-00 

Phosphorus P  31-00 

Chlorine Cl  35-46 

Potassium K  39-14 

Sodium Na  23'04 

Magnesium Mg  24-00 

Calcium Ca  40-00 

Iron Fe  56 '00 

In  addition  to  these  twelve  principal  elements,  other  elements 
occur,  but  in  relatively  smaller  quantities ;  they  are  not  present 
in  every  cell,  but  only  in  certain  special  plants  and  animals. 
These  are : — 

Name.  Symbol.         Atomic  Weight. 

Silicon Si  28-19 

Fluorine         .         .         .         .         .  F  18-98 

Bromine          .         .         .                  .  Br  79  76 

Iodine I  126-55 

Aluminium Al  27'00 

Manganese     .....  Mn  53-90 

Lithium                           ..."  Li  7'00 


20  ,  PHYSIOLOGY  CHAP. 

Name.  Symbol.       Atomic  Weight. 

Copper Cu  63-17 

Lead Pb  206-47 

Zinc Zn  64-90 

With  the  exception  of  silicon,  which  is  widely  distributed  in 
both  kingdoms,  fluorine,  which  in  small  but  constant  quantities 
enters  into  the  chemical  composition  of  the  enamel  of  the  teeth, 
and  iodine,  which  has  lately  been  found  in  one  of  the  constituents 
of  the  thyroid  gland,  it  is  probable  that  all  these  elements  are 
without  physiological  significance  to  the  ceJl-body  in  which  they 
are  found,  and  that  they  enter  accidentally,  like  many  other 
extraneous  elements,  e.g.  drugs,  toxins,  or  such  as  are  merely 
indifferent  bodies. 

It  is  worth  noting  that  the  twelve  principal  elements  that  enter 
constantly  into  the  composition  of  cells  have  all  a  low  atomic 
weight.  Nine  of  them,  in  fact,  belong  to  the  first  three  series  of 
Mendelejeff  s  Periodic  System,  and  only  three  (potassium,  calcium, 
iron)  belong  to  the  fourth  series  of  the  system.  Further,  these 
are  all  found  either  in  the  state  of  elements  or  as  very  simple 
inorganic  combinations,  which  are  widely  diffused  in  the  air,  in 
water,  and  in  the  upper  layers  of  the  soil — the  only  habitat  of  flora 
and  fauna. 

VI.  The  chemical  compounds  of  which  the  cell  is  built  up  may 
be  divided  into  organic  and  inorganic.  Organic  substances  are 
distinguished  as  nitrogenous  and  non-nitrogenous ;  the  former 
include  the  Proteins  and  their  derivatives,  the  latter  the  Fats  and 
Carbohydrates. 

Proteins  are  the  most  important  organic  substances,  and  are 
indispensable  in  the  constitution  of  living  protoplasm.  They  are 
essentially  distinct  from  carbohydrates  and  fats  in  their  element- 
ary composition,  for  in  addition  to  carbon,  hydrogen,  and  oxygen 
they  contain  nitrogen  and  sulphur.  Their  molecular  structure, 
and  the  exact  number  of  atoms  of  the  several  elements  which 
enter  into  their  constitution,  are  still  unknown  to  us.  There  is, 
however,  no  doubt  that  the  molecular  structure  of  these  sub- 
stances is  highly  complex ;  more  so,  perhaps,  than  that  of  any 
other  chemical  substance,  since  the  ratio  of  the  number  of  the 
various  atoms  reaches  a  very  considerable  figure. 

It  should  be  noted  that  the  five  elements  above  mentioned  are 
found  in  the  different  proteins  in  much  the  same  proportions, 
as  appears  from  the  following  table,  which  gives  the  limits 
between  which  the  percentages  of  the  various  elements  of  protein 
oscillate : — 

C  50     —  55    mean  52  per  cent. 
H    9-5-    7-3     „       7       „ 
N15    -17-6     „     16       „ 
O  19     -24        „     23       „ 
S    0-3  -    2-4  2 


i  LIVING  MATTEE  21 

These  figures,  of  course,  throw  no  light  on  the  grouping  of  the 
respective  elements;  i.e.  the  chemical  structure  of  the  protein 
molecule.  They  show,  however,  that  the  different  proteins  form 
a  well-defined  class  of  chemical  compounds,  having  a  strict 
relation  among  themselves,  as  is  further  apparent  from  the 
physico-chemical  properties  common  to  the  several  members,  as 
follows  : — 

(a)  Non-diffusibility  through  the  pores  of  animal  or  vegetable 
membranes  and  of  artificial  parchment ;  they  belong,  therefore,  to 
the  class  of  bodies  which  Graham  termed  colloids.  They  are 
obtained  in  a  crystalline  form  with  difficulty,  and  only  by  special 
methods.  If  the  colloid  is  fluid  it  is  termed  sol;  if  solid,  gel. 
Liquid  and  solid  gelatin  are  examples  of  these  two  states. 
When  water  is  the  medium  in  which  the  colloid  is  dispersed  the 
terms  hydrosol  and  hydrogel  are  used  respectively.  Besides  the 
proteins,  many  inorganic  substances  can  exist  in  a  colloidal  form, 
e.g.  colloidal  metals,  silicic  acid,  etc.  There  has  been  much  recent 
discussion  as  to  the  state  in  which  the  colloids  exist  in  a  solvent 
(which  in  the  case  of  the  proteins  of  the  living  body  is  exclusively 
represented  by  water).  According  to  the  latest  conclusions,  we 
are  here  concerned  not  with  true  solutions — having  the  well-known 
properties  of  solutions,  due  to  the  mixing  of  the  soluble  crystalloids, 
salts,  urea,  glucose,  etc.,  with  water — but  rather  with  very  fine 
emulsions  or  suspensions,  i.e.  the  particles  of  the  colloid  substance 
can  be  seen  in  a  separate  state,  suspended  in  the  liquid,  and  do 
not  enter  into  those  intimate  relations  with  the  solvent  on  which 
depend  the  physico-chemical  characters  of  true  solutions  (osmotic 
pressures,  homogeneity  under  high  magnification,  etc.).  In  fact, 
these  colloidal  solutions  scarcely  lower  the  freezing-point  of  the 
solvent,  and  under  the  ultra-microscope  a^re  seen  to  consist  of 
various-sized  granules  moving  in  the  body  of  the  fluid. 

(6)  All  proteins  have,  further,  very  definite  chemical  properties, 
by  which  they  are  sharply  differentiated  from  all  other  known 
chemical  aggregates,  crystalloids  or  colloids.  Their  aqueous 
solutions  are  optically  active,  since  they  deflect  the  plane  of 
polarised  light  to  the  left.  Heat,  the  addition  of  small  quantities 
of  mineral  acid,  salts  of  the  heavy  metals,  as  also  absolute  alcohol, 
solutions  of  tannin,  phosphotungstic  acid,  picric  acid,  etc.,  pre- 
cipitate and  often  coagulate  them  (albumins  and  globulins).  In 
this  case  the  protein  molecule  undergoes  profound  changes,  for 
after  removal  of  the  precipitating  agfent  the  initial  state  of  col- 
loid cannot  be  restored ;  the  protein  is  said  to  be  de-natured. 
Proteins  are  further  precipitated  by  saturation  of  the  solvent  with 
salts  of  the  alkalies  or  alkaline  earths  (sodium  chloride,  magnesium 
sulphate,  ammonium  sulphate).  It  is  important  in  the  chemistry 
of  the  proteins  to  note  that  in  the  precipitation  determined  by 
these  salts  the  proteins  are  not  de-natured,  or  at  any  rate  become 


22  PHYSIOLOGY  CHAP. 

so  very  much  more  slowly — for  they  re-dissolve  on  removal  of  the 
salts  by  which  they  were  precipitated. 

All  proteins  give  specific  colour  reactions.  The  best  known 
are  the  following  : — 

Millon's  Reaction. — On  adding  a  solution  of  mercuric  and 
mercurous  nitrate  and  nitrite  in  nitric  acid  (Millon's  reagent)  and 
heating,  the  white  precipitate  first  formed  turns  red. 

Xanthoproteic  Reaction. —  On  heating  with  nitric  acid  the 
solution  of  protein  turns  yellow,  and  then,  on  the  addition  of 
ammonia,  orange. 

Molisch's  Reaction. — On  adding  a  few  drops  of  a-naphthol 
and  running  in  concentrated  sulphuric  acid,  under  the  solution,  a 
violet  ring  appears  at  the  junction  of  the  two  fluids.  If  alcohol, 
ether,  or  potash  be  now  added  it  turns  yellow.  The  substitution 
of  thymol  for  a-naphthol  gives  a  fine  rose  carmine,  which  gradu- 
ally becomes  green. 

Biuret  Reaction. — A  few  drops  of  2  per  cent  copper  sulphate 
added  to  a  solution  of  protein  made  alkaline  with  caustic  potash 
or  soda,  produces  a  clear  violet  colour  in  the  cold.  Proteoses  and 
peptones,  which  are  the  primary  decomposition  products  of  the 
more  complex  proteins  formed  by  the  action  of  proteolytic  fer- 
ments (infra],  give  a  pure  pink  colour,  r 

Sulphur  Reaction. — On  warming  with  potash  and  a  little  lead 
acetate,  the  white  precipitate  which  first  appears  (lead  hydroxide) 
turns  brown  and  then  black,  owing  to  the  formation  of  lead 
sulphide. 

These  colour  tests  for  proteins  are  important,  not  merely  as 
showing  the  presence  of  protein,  but  because  they  prove  the 
existence  in  the  complex  molecule  of  certain  definite  chemical 
compounds  to  which  the  several  reactions  are  due.  The  sulphur 
test,  e.g.,  indicates  the  presence  of  cystine  which  contains  this 
element ;  Millon's  test,  of  the  tyrosine  group ;  the  xanthoproteic 
test,  of  aromatic  groups ;  Molisch's  reaction,  of  a  carbohydrate  : 
and  so  on.  In  fact,  these  chemical  aggregates  respectively  always 
give  these  identical  reactions,  which  are  accordingly  known  as 
"  constitutional  tests."  The  biuret  reaction  is  the  most  general 
test  for  proteins,  since  it  is  given  by  all  the  proteins  and  their 
most  immediate  derivatives  (the  proteoses  and  peptones).  It  is 
given  by  biuret  and  other  compounds  which  contain  CO.NH 
groups.  It  is  also  given  by  some  of  the  less  complex  derivatives 
(polypeptides),  but  not  by  the  ultimate  products  of  their  decomposi- 
tion (amino -acids). 

VII.  Owing  to  our  inadequate  knowledge  of  the  exact  chemical 
constitution  of  the  different  proteins  their  classification  is  still 
based  principally  upon  their  physical  or  physico-chemical 
properties,  e.g.  solubility  in  water  or  in  certain  salt  solutions,  the 
temperature  at  which  they  coagulate,  etc.  The  Chemical  and 


i  LIVING  MATTEE  23 

Physiological  Societies  of  Great  Britain  adopted   the  following 
scheme  of  classification  in  1907  1 : — 

I.  Protamines,  e.g.  salmine,  sturine. 
II.  Histories,  e.g.  thymus  histone. 

III.  Albumins,  e.g.  ovalbumin,  serum  albumin,  various  vegetable  albumins. 
IV.  Globulins,  e.g.  serum  globulin,  fibrinogen  and  fibrin,  myosinogen  and 

myosin.     Vegetable  globulins. 
V.  Glutelins,  e.g.  wheat  glutelin) 

VI.  Gliadins,  *./  wheat  gliadin    /Present  only  in  cereals. 
VII.  Phosplioproteins,2  e.g.  caseinogen,  vitellin,  ichthulin. 
VIII.  Scleroproteins,3    e.g.    collagen   and   gelatin,    keratin,    elastin,    fibroin, 

spongin,  amyloid,  albumoid,  pigments. 

IX.  Conjugated  proteins.     These  are  combinations  of  protein  with  other 
compounds. 

(a)  Nucleoproteins. 
(6)  Chromoproteins,  e.g.  haemoglobin. 
(c)  Glucoproteins. 

X.  Derivatives  of  proteins.     These  are  formed  from  members  of  the  other 
groups  by  the  action  of  acids  and  alkalies,  or  enzymes. 

(«)  Metaproteinj^f^n. 

(6)  Proteoses  :  album ose,  globulose,  caseose,  gelatose,  etc. 

(c)  Peptones,  e.g.  fibrin  peptone,  caseo-peptone,  etc. 

(d)  Polypeptides,  e.g.  glycyl-1-tyrosine,  d-alanyl-glycine,  1-leucyl- 

d-glutamic  acid,  d-alanyl-1-leucine,  etc.  The  majority  are 
synthetical  compounds.  Several  have  now  been  isolated 
from  proteins. 

Albumins  are  coagulable  proteins,  soluble  in  distilled  water,  in 
dilute  salt  solutions,  in  acids  and  bases,  and  they  are  not  precipi- 
tated by  saturating  the  solutions  with  neutral  sodium  chloride  or 
magnesium  sulphate  when  the  solution  'is  neutral,  but  they  are 
precipitated  by  these  salts  when  the  solution  is  acid.  They  are 
precipitated  by  saturating  the  solution  with  ammonium  sulphate. 

Globulins  are  coagulable  proteins,  insoluble  in  distilled  water 
and  dilute  acids,  soluble  on  the  other  hand  in  solutions  of  neutral 
salts  and  dilute  bases.  They  are  precipitated  on  saturation  with 
magnesium  sulphate  and  to  a  certain  extent  with  sodium  chloride ; 
with  ammonium  sulphate  they  are  precipitated  at  a  lower  degree 
of  concentration  (  =  J  saturation)  than  that  required  to  precipitate 
albumin. 

The  vegetable  globulins  differ  in  many  respects  from  the  animal 
globulins ;  they  have  a  great  tendency  to  crystallise,  and  'have 
been  prepared  in  large  quantities  in  a  crystalline  form  (Osborne). 

Fibrinogen  and  myosin  will  be  discussed  in  the  chapters  on 
Blood  Plasma  and  Muscle. 

Phosphoproteins  are  characterised  by  the  fact  that  phosphorus 
enters  into  their  composition,  so  that  formerly  they  were  erroneously 
classed  with  the  nucleoproteins.  They  are  distinct  from  these 

1  Substituted  by  translator  for  0.  Cohnheim's  (1904)  scheme. 

2  Formerly  nucleoalbumins.  "   3  Formerly  albuminoids. 


24  PHYSIOLOGY  CHAP. 

inasmuch  as  they  contain  no  xanthine  or  purine  bases,  which  are 
characteristic  of  nucleoproteins.  They  differ  from  nucleoproteins 
also  in  that  the  phosphorus  is  completely  removed,  as  inorganic 
phosphoric  acid,  by  treatment  with  1  per  cent  caustic  soda  at  37°  C. 
for  24  hours  (Plimmer  and  Scott).  The  phosphoproteins  have  the 
properties  of  acids;  they  turn  blue  litmus  paper  red,  and  arp 
soluble  in  distilled  water  only  in  the  form  of  their  alkaline  salts, 
from  which  solutions  they  can  be  precipitated  by  the  addition  of 
stronger  acids.  Solutions  of  their  salts  do  not  coagulate  with 
heat. 

Histones,  on  the  contrary,  have  the  character  of  weak  bases, 
their  solutions  being  precipitated  by  alkalies. 

The  protamines  form  a  very  definite  group,  differentiated  in 
not  a  few  particulars  from  the  rest  of  the  proteins :  they  do  not 
contain  sulphur,  and  are  richer  in  nitrogen  and  poorer  in  carbon 
than  the  other  proteins.  They  are  distinctly  basic  in  character, 
more  so  than  the  histones.  They  have  been  isolated  from  the 
spermatozoa  of  many  fishes  (salmine,  clupine,  scombrine,  sturine, 
etc.). 

We  shall  deal  with  the  derivatives  of  the  proteins,  more 
particularly  with  the  proteoses  and  peptones,  which  result  from  the 
action  of  the  proteoly tic  ferments  on  Ihe  more  complex  proteins, 
in  the  chapter  on  Digestion. 

The  conjugated  proteins  are  combinations  of  a  protein  with 
a  chemical  aggregate,  which  is  not  a  protein,  and  which  Hoppe- 
Seyler  termed  a  "  prosthetic  group."  In  the  nucleoproteins  dis- 
covered by  Miescher  and  Bloss  (1871)  in  cell-nuclei,  this  prosthetic 
group  is  represented  by  nucleic  acid :  nucleoprotein  therefore 
results  from  a  combination  of  protein  and  nucleic  acid.  The 
nucleic  acids  are  organic  acids  which  contain  phosphorus  and 
nitrogen,  but  no  sulphur,  their  chemical  constitution  being  un- 
known. Their  decomposition  products,  on  the  contrary,  are  known 
to  us :  these  are  phosphoric  acid,  purine  bases  (adenine,  guanine, 
hypoxanthine,  and  xanthine),  pyrimidine  bases  (thymine,  uracil, 
cytosine),  pentoses  (laevulinic  acid). 

Of  the  various  proteins  which  are  able  to  unite  with  the  nucleic 
acids  to  form  nucleoprotein,  the  protamines  and  histones  are  the 
principal.  These  enter  into  the  molecules  of  the  nucleoproteins  of 
fishes'  testicles.  Nucleic  acid  is  also  combined  with  histone  in 
the  leucocytes  of  the  thymus  and  the  nucleated  red  corpuscles. 

Nucleoproteins  have  distinct  acid  properties :  they  are  soluble 
in  water  and  in  saline  solutions,  still  more  in  alkaline  fluids ; 
they  are  precipitated  on  the  addition  of  acids,  but  are  redissolved 
by  excess  of  mineral  acid. 

Haemoglobin  (to  which  we  shall  return  in  discussing  Blood) 
results  from  the  combination  of  a  histone  (globin)  and  a  complex 
chemical  aggregate  containing  iron  (haematin). 


i  LIVING  MATTER  25 

Glucoproteins  are  conjugated  proteins,  consisting  of  a  carbo- 
hydrate radicle  combined  with  protein.  The  nature  and  consti- 
tution of  this  carbohydrate  group  is  unknown.  It  appears  to  be 
a  polysaccharide,  since  it  does  not  reduce  :  it  contains  an  ammo 
group  (NH2),  for  when  boiled  with  acids,  it  usually  yields  gluco- 
samine. 

The  group  of  proteins  known  as  the  scleroproteins  includes  a 
series  of  substances  which  have  few  physical  properties  in  common 
with  the  preceding  groups,  but  share  many  other  characters  with 
them.  They  never  form  part  of  the  animal  cell,  but  compose  the 
skeletal  or  supporting  substance  for  the  cells  and  organs  of  the 
body:  they  belong  to  the  histological  group  of  the  connective 
tissues  in  the  widest  sense  of  that  term.  There  are  no  sclero- 
proteins in  the  tissue  fluids  of  animals'  blood,  lymph,  etc.  The 
concept  scleroprotein  is  essentially  morphological,  and  from  a 
chemical  point  of  view  includes  most  various  bodies. 

As  proteins,  the  scleroproteins  have  many  properties  in  common 
with  the  other  groups.  By  the  action  of  acids  or  of  proteolytic 
ferments  they  are  split  into  proteoses,  peptones,  and  amino-acids  ; 
they  form  salts  ;  and  they  have  the  same  percentage  composition 
and  give  the  same  colour  reactions. 

Of  the  various  scleroproteins  enumerated  in  the  table,  we  may 
say  that  collagen  is  the  general  substance  of  bone,  cartilage,  and 
connective  fibres ;  on  boiling,  it  takes  up  water  and  is  transformed 
into  gelatin.  Keratin,  the  ground  substance  of  the  cornea,  is  an 
elaboration  product  of  the  epidermic  cells  of  the  cutis.  Elastin,  a 
component  of  the  fibres  of  elastic  tissue  and  the  ligamentum 
nuchae,  is  a  product  of  connective  tissue  cells.  Fibroin,  the 
principal  component  of  silk,  is  an  elaboration  product  of  the 
spinning  gland  of  the  silkworm.  Spongin  is  the  organic  support- 
ing substance  of  the  bath  sponge.  Conchiolin  is  the  organic  matrix 
of  the  snail  and  other  molluscs.  Amyloid,  lastly,  is  a  substance 
which  is  absent  in  the  healthy  organism,  but  accumulates  in 
enormous  quantities  under  the  influence  of  various  pathological 
degenerative  processes. 

Albumoid  is  the  name  which  has  been  given  to  many  different 
substances  found  in  various  organisms,  e.g.  the  membrana  propria 
of  certain  glands,  the  vitreous  membrane,  sarcolernma,  the  solid 
constituents  of  the  lens,  scales  of  fishes,  etc.  These  are  also 
scleroproteins. 

Lastly,  the  group  of  pigments,  or  melanin s,  includes  all  those 
various  pigments,  brown,  black,  chestnut,  etc.,  which  determine 
the  characteristic  hue  of  hair,  fur,  and  choroid,  and  which  are  found 
in  the  so-called  melanotic  tumours. 

VIII.  The  analytical  and  experimental  work  on  the  chemical 
structure  and  constitution  of  proteins,  as  recently  carried  out  by 
such  distinguished  physiological  chemists  as  Kossel,  Hofmeister, 


26  PHYSIOLOGY  CHAP. 

and  more  particularly  Fischer  and  his  school,  has  led  within  the 
last  few  years  to  important  results.  While  these  do  not  as  yet 
account  fully  for  all  the  different  chemical  units  which  build 
up  the  complex  protein  molecule,  they  represent  a  great  advance 
in  this  direction.  A  brief  review  of  this  work,  which  has 
profoundly  modified  most  of  the  theories  previously  held  by 
physiologists,  is  essential. 

The  analytical  method  is  invariably  employed  in  investigating 
the  chemical  structure  of  highly  complex  bodies.  The  complex 
substance  must  be  decomposed  and  split  up  into  its  simpler 
constituents,  i.e.  into  the  units  of  which  it  is  built  up.  For 
proteins,  hydrolytic  cleavage  is  the  method  of  artificial  decom- 
position that  gives  the  best  results,  i.e.  decomposition  with 
absorption  of  molecules  of  water.  This  hydrolytic  cleavage  or 
hydrolysis  of  proteins  may  take  place  by  the  prolonged  action— 

(a)  Of  mineral  acids,  by  boiling  the  protein  with  concentrated 
hydrochloric  acid  or  25  per  cent  sulphuric  acid  for  twelve  to  fifteen 
hours  (method  proposed  by  Fischer,  and  generally  used  in  his 
laboratory) ; 

(6)  Of  alkalies ;  and 
(c)  Of  proteoly tic  ferments. 

The  most  important  result  of  all  the  researches  in  to1  hydrolytic 
cleavage  up  to  the  present  time  is  that  even  the  most  unlike 
proteins  have,  among  themselves,  a  very  similar  constitution, 
judging  from  the  end  products.  These  are  invariably  the  same, 
no  matter  what  process  of  hydrolytic  decomposition  is  employed. 
It  was  formerly  believed  that  one  essential  difference  only  existed 
between  hydrolysis  by  the  proteoly  tic  ferments  and  that  by  acids 
and  alkalies':  the  disintegrating  action  of  the  ferments  was 
supposed  to  be  more  gradual,  since  before  reaching  the  final 
products  of  cleavage,  which  no  longer  yield  the  biuret  reaction, 
those  intermediate  cleavage  products  were  obtained  which  are 
known  by  the  name  of  proteoses  and  peptones  (of  which  we  shall 
treat  fully  in  the  physiology  of  Digestion).  These  products  were 
supposed  not  to  appear  in  the  cleavage  effected  by  strong  acids 
and  bases,  but  complex  products  with  similar  properties  have  now 
been  isolated  and  studied  by  Fischer  and  Abderhalden.  Some  of 
the  final  products  of  cleavage  are  still  unknown  ;  most  of  them, 
however,  have  been  isolated  and  identified.  They  are  the  organic 
'  compounds  known  as  amino-acids,  or  organic  acids,  in  the  molecule 
of  which  an  amino-group  (NH2)  is  substituted  for  one  or  more 
atoms  of  hydrogen  ;  our  knowledge  of  the  various  amino-acids  that 
arise  from  proteins  by  cleavage  is  mainly  due  to  Fischer,  who  has 
devised  new  methods  for  their  isolation  and  recognition.  The 
number  and  variety  of  the  amino-acids  at  present  isolated  is  shown 
in  the  following  table  of  Abderhalden  : — 


i  LIVING  MATTER  27 

I.  Aliphatic  or  Fatty  Series. 

1.  Mono-aniino-mono-carboxylic  acids  :  glycine 

alanine 
valine 
leucine 
isoleucine. 

2.  Mono-amino-oxy-mono-carboxylic  acids  :  serine. 

3.  Mono-amino-tliio-mono-carboxylic  acids  :  cysteine  and  cystine. 

4.  Mono-amino-di-carboxylic  acids  :  aspartic  acid 

glutamic  acid. 

5.  Di-amino-moiio-carboxylic  acids  :  lysine 

arginine. 

6.  Di-amino-oxy-mono-carboxylic  acids  :  di-arnino-tri-oxy-dodecanic  acid. 

II.  Aromatic  Series. 

1.  Mono-amino-mono-carboxylic  acids  :  phenylalanine. 

2.  Mono-amino-oxy-mono-carboxylic  acids  :  tyrosine. 

III.  Heterocyclic  Compounds. 

1.  Mono-amino-mono-carboxylic  acids:  proliiie  (a-pyrrolidine-carboxylic  acid) 

tryptophane    (indole  -  a  -  ammo  -  pro- 

pionic  acid) 
liistidine    (imidazole  -  a  -  ammo  -  pro- 

pionic  acid). 

2.  Mono-amino-oxy-mono-carboxylic    acids  :    oxy -proliiie    (oxy-pyrrolidine- 

carboxylic  acid). 

Some  chemists  further  regard  the  carbohydrate  (glucosamine) 
group  as  a  cleavage  product  of  proteins  :  this  group,  however, 
occupies  a  special  position,  inasmuch  as  it  is  absent  in  many 
proteins,  while  in  others  its  presence  is  doubtful,  and,  moreover, 
those  which  contain  large  amounts  of  it  'are  by  many  considered 
to  be  compound  proteins  (gluco-proteins).  We  may  suppose  that 
as  all  proteins  contain  units  which  exhibit  great  affinity  to  the 
molecule  of  a  carbohydrate,  since  they  contain  six  carbon  atoms, 
there  is  a  possible  transition  from  this  group  to  the  carbohydrate 
molecule.  Lysine,  e.g.,  which  is  an  amino-acid  invariably  present 
among  the  cleavage  products  of  all  proteins,  has  a  formula  very 
like  that  of  glucosamine  and  glucose,  as  will  be  seen  from  the 
following  table  : — 

CH2(OH)  CH2(OH)  CH2(NH2) 

CH(OH)  CH(OH)  CH2 

CH(OH)  CH(OH)  CH2 

CH(OH)  CH(OH)  CH, 

( '  1 


CH(OH)  CH(NH2)  CH(NH2) 

CH : 0  COOH 


CH:  0 


Glucose  Glucosamine  Lysine 


28  PHYSIOLOGY  CHAP. 

Keturning  to  the  various  amino-  acids  which  represent  the 
products  of  the  hydroly  tic  cleavage  of  proteins,  we  must  note  the 
important  fact  that,  with  the  exception  of  the  protamines,  all 
proteins  hitherto  decomposed  contain  the]  same  units.  One  or 
other  of  the  amino-acids,  e.g.  glycine  in  egg  albumin  and  serum 
albumin,  may  be  wanting,  but  these  are  rare  exceptions. 

What  differentiates  the  several  proteins  among  themselves  is, 
on  the  other  hand,  the  varying  quantitative  relations  of  the  differ- 
ent amino-acids  which  compose  the  protein  molecule.  In  some 
proteins,  certain  special  amino-acids,  e.g.  leucine  and  more  particu- 
larly glutamic  acid,  occur  in  enormous  quantities,  as  in  the 
proteins  of  plant  seeds.  There  are  great  differences,  again,  in  the 
relative  proportions  of  the  mono-  and  di-amino  acids ;  the  latter 
are  found  in  large  quantities  in  the  protamines,  while  they  are 
almost  absent  in  some  of  the  scleroproteins. 

The  histones  occupy  an  intermediate  position  between  the  pro- 
tamines and  the  coagulable  proteins  (albumins  and  globulins). 

From  these  facts  it  may  be  anticipated  that  we  shall  before  long 
be  able  to  classify  the  various  groups  of  proteins  on  the  basis  of 
similar  end  products.  Indeed,  from  the  fact  that  the  same  units 
enter  into  their  constitution,  although  in  different  proportions  for 
the  different  substances,  we  can  even"  now  to  a  certain  extent 
perceive  how  the  several  alimentary  proteins  may  be  converted 
into  the  other  definite  proteins  of  the  animal  body. 

It  has  been  objected  that  the  ultimate  cleavage  products  of 
the  artificial  hydrolysis  of  proteins  are  not  really  pre-formed  as 
so  many  units  in  the  protein  molecule :  but  the  various  data 
recently  acquired  meet  this  objection.  The  following  may  be 
briefly  noted  :— 

(a)  In  whatever  way  the  hydrolytic  cleavage  of  any  protein  is 
effected,  whether  by  acids,  by  alkalies,  or  by  proteolytic  ferments, 
the  final  products  are  approximately  the  same  in  quality   and 
quantity.     Tryptophane  is  the  sole  exception,  since  it  is  largely 
destroyed  on  hydrolysis  by  acids. 

(b)  Fischer   has   succeeded   in   artificially  combining  two  or 
more  molecules  of  amino-acid,  and  has  thus  obtained  synthetically 
the  chemical  compounds  which  he  terms  polypeptides,  which  in  a 
number  of  properties  have  affinity  with  the  natural  proteins.     The 
type  on  which  this  synthesis  has  been  successfully  carried  out  is 
represented  by  the  simplest  dipeptide,  which  is  known  as  glycyl- 
glycine,  and  which  results  from  the  coupling   together   of  two 
molecules   of  glycine  (or  glycocoll)   according  to   the   following 
equation : — 

NH2.CH2.COOH  +  HNH.CH2.COOH  = 

glycine  glycine 

NH2.CH2.CO.NH.CH2.COOH  +  H20.  ; 

glycyl-glycine 


i  LIVING  MATTEE  29- 

Here  the  basic  group  (NH2)  of  one  molecule  of  glycine  is 
united  with  the  acid  group  (COOH)  of  the  second,  with  loss  of  a 
molecule  of  water — a  true  polymerisation.  It  is  clear  that  by  the 
same  process  another  molecule  of  glycine  may  be  united  with  this- 
compound  (dipeptide),  thus  making  a  tripeptide,  and  so  on.  If 
we  remember  that  all  other  amino-acids  are  capable  like  glycine 
of  similar  combination  between  themselves  and  with  the  molecules 
of  other  amino-acids,  it  is  evidently  possible  to  obtain  a  very 
numerous  series  of  different  and  more  or  less  highly  complex 
compounds. 

Fischer  and  his  school  have  already  succeeded  in  producing 
synthetically  some  seventy  similar  compounds  ;  the  most  complex 
is  an  octadecapeptide,  which  consists  of  eighteen  molecules  of 
amino-acid  united  together  in  this  manner. 

It  is  important  to  note  that  many  of  these  polypeptides, 
particularly  the  more  complex,  give  the  biuret  reaction,  which,  as- 
we  have  said,  is  the  most  characteristic  test  of  protein,  and  that 
some  of  them  are  digested  by  pancreatic  juice,  which  disintegrates- 
them  into  the  amino-acid  components,  as  is  the  case  with  natural 
proteins. 

IX.  Enzymes  and  ferments  must  further  be  included  in  the- 
protein  group,  and  belong  in  all  probability  to  the  nucleoproteins, 
or,  according  to  others,  the  scleroproteins.  These,  being  elabora- 
tion products  of  the  living  cell,  represent,  according  to  the  latest 
view  (Hofmeister,  1901),  the  chemical  instruments  by  means  of 
which  all  chemical  changes  of  the  different  substances  which 
form  the  material  substratum  of  living  matter  take  place.  These 
chemical  changes  result  in  the  disintegration  of  the  complex 
molecule  into  simpler  compounds  (cleavage  by  analytical  ferments),, 
either  by  rendering  it  suitable  in  form  and  quality  for  assimilation, 
as  in  the  case  of  the  various  digestive  ferments  of  the  alimentary 
canal  in  animals,  or  by  setting  free  the  potential  energy  which  is 
manifested  in  the  form  of  heat  or  movement.  To  this  large  class 
of  analytic  ferments  another  class  of  ferments  is  opposed,  whose 
work  consists  not  in  the  chemical  cleavage  of  substances  with 
large  molecules,  but  in  synthetic  processes,  in  which  simple 
molecules  unite  to  form  more  complex  molecules,  as  occurs  in  the 
so-called  anabolic  phase  of  metabolism  in  living  organisms.  The 
theoretical  existence  of  these  supposed  synthetic  ferments  has  so 
far  not  received  any  decisive  proof.  We  will  therefore  content 
ourselves  with  a  rapid  survey  of  the  class  of  analytic  ferments,  of 
which  much  has  been  learnt  by  recent  work. 

The  fermentative  processes  of  decomposition  were,  until  recently,, 
divided  into  two  great  classes  which  were  very  distinct  from  one 
another.  In  the  one  class  were  placed  all  the  non-organised 
ferments  or  enzymes,  which  were  regarded  as  the  elaboration  pro- 
ducts of  the  various  secreting  glands,  capable  of  being  isolated,, 


30  PHYSIOLOGY  CHAP. 

and  of  acting  as  pure  chemical  agents,  independent  of  the  living 
elements  which  produced  them.  The  several  digestive  enzymes 
of  the  gastro  -  intestinal  tract  in  animals  were  considered  as 
examples  of  these  non-organised  ferments. 

The  second  class  comprised  the  so-called  organised  ferments,  or 
ferments  proper,  represented  by  micro-organisms  (fungi,  bacteria, 
etc.),  the  action  of  which  was  then  held  to  be  in  direct  dependence* 
upon  the  vitality  of  the  latter,  and  to  cease  on  their  death  or 
disorganisation.  Saccharomyces  cerevisiae,  which  determines  the 
alcoholic  fermentation  of  glucose  (Pasteur),  was  regarded  as  the 
prototype  of  such  organised  ferments. 

Now,  however,  in  consequence  of  Buchner's  work  (1899),  this 
distinction  can  no  longer  be  maintained.  Buchner  has  demon- 
strated experimentally  that  it  is  possible  to  extract  from  the  cells 
of  beer-yeast,  when  exposed  to  enormous  pressure,  a  substance  rich 
in  protein,  which  is  free  from  Jiving  elements,  and  is  able  to  set 
up  the  alcoholic  fermentation  of  solutions  of  glucose.  The 
property  by  which  yeast  cells  ferment  glucose  is  therefore  due, 
not  to  a  true  vital  process,  but  to  the  action  of  an  enzyme  or 
zymase,  produced  by  the  cell.  Specific  enzymes  of  other  micro- 
organisms formerly  held  to  be  organised  ferments  (the  bacilli  of 
lactic  fermentation,  of  acetic  fermentation,  etc.)  have  .also  been 
isolated. 

All  enzymes  are  now  regarded  as  organic  substances  (most 
probably  of  the  nature  of  proteins)  which  are  elaboration  products 
of  the  living  cells,  from  which  they  can  be  separated  and  extracted 
by  various  methods  without  losing  their  activity.  Generally 
speaking  they  can  be  extracted  from  the  cells  and  the  tissues,  on 
treating  these  with  water  or  glycerin.  The  latter  solvent,  in 
particular,  yields  solutions  that  remain  active  for  a  considerable 
time,  and  has  been  largely  employed  in  practice  to  extract  these 
•enzymes. 

It  should  be  stated  that  the  enzymes  are  frequently  not  found 
pre-formed  within  the  cells  which  produce  them,  but  are  as  it  were 
in  a  potential  state.  The  complete  development  of  their  specific 
enzyme  activity  necessitates  the  further  action  of  oxygen  and 
other  chemical  compounds  known  as  kinases.  The  mother- 
substances  from  which  the  enzymes  are  derived  are  called 
zymogens  or  pro-enzymes.  We  shall  discuss  these  at  length  in 
'speaking  of  the  digestive  ferments,  since  there  is  in  the  intestine 
a  substance  which  activates  the  pancreatic  enzymes  (enter  o-kinase). 

No  characteristic  chemical  reactions  are  common  to  all  enzymes; 
generally  speaking,  they  are  precipitated  from  their  colloidal 
solutions  by  alcohol,  and  are  destroyed  by  high  temperatures  from 
+  80°  to  +  100°  C.  In  order  to  recognise  them,  it  is  necessary 
to  observe  the  properties  which  characterise  their  mode  of 
action.  In  the  first  place  enzymes,  in  consequence  of  their 


i  LIVING  MATTEE  31 

peculiar  chemical  action,  do  not  form  stable  combinations  with 
the  substances  on  which  they  act,  or  with  the  decomposition 
products  arising  from  their  activity.  An  infinitesimal  quantity  of 
enzyme  is  able  to  act  upon  a  relatively  enormous  quantity  of 
fermentable  substance.  It  has  been  found,  e.g.,  that  one  part  of 
invertase  is  capable  of  splitting  up  100,000  parts  of  saccharose, 
and  one  part  of  chymosin  or  rennet  of  coagulating  400,000  parts 
of  caseinogen. 

A  second  property  of  enzymes  is  the  specific  character  of  their 
action,  inasmuch  as  any  one  enzyme  acts  only  upon  a  definite 
substance,  or  upon  a  restricted  group  of  allied  substances.  Enzyme 
action  is  always  in  strict  relation  with  the  configuration  and  con- 
stitution of  the  atomic  grouping  of  the  relative  molecules,  to 
which  the  enzyme  is  as  rigorously  adapted  as  the  key  to  the  wards 
of  a  lock — to  repeat  once  more  the  picturesque  expression  of  E. 
Fischer.  This  specific  action  is,  in  fact,  so  conspicuous  as  to  serve 
as  a  method  of  distinguishing  isomeric  chemical  compounds  from 
one  another. 

Enzyme  action  is  further  influenced  by  various  external 
conditions,  e.g.  the  reaction  of  the  liquid :  some  ferments  are 
active  only  in  an  acid  medium,  others — and  far  the  greater  number 
— in  a  neutral  or  faintly  alkaline  medium. 

Temperature  has  a  marked  influence  on  the  course  of  enzyme 
activity,  which  usually  increases  with  the  rise  of  temperature 
to  a  certain  point  representing  the  optimum,  after  which  a 
further  rise  of  temperature  diminishes  the  enzyme  action  until 
it  disappears. 

The  accumulation  of  cleavage  products  has  a  marked  inhibitory 
influence  on  the  development  of  enzyme  activity ;  the  inhibition 
ceases  so  soon  as  these  products  are  removed. 

How  is  it  possible  to  explain  the  action  of  enzymes  ? 

Certain  inorganic  substances  exhibit  properties  highly  similar 
to  those  of  the  analytical  enzymes  we  have  been  considering,  since 
they  are  capable  of  producing  cleavage  processes  which  do  not 
essentially  differ  from  processes  of  fermentation.  These  sub- 
stances, which  have  been  known  for  some  time  to  chemists,  are 
the  so-called  catalysers,  and  determine  the  process  of  catalysis 
(Ostwald).  A  classical  example  of  catalytic  action  is  that  repre- 
sented by  the  decomposition  of  hydrogen  peroxide  (H202)  into 
oxygen  (0)  and  water  (H2O)  by  platinum  black.  A  trace  of  this 
substance  will  decompose  an  enormous  amount  of  hydrogen 
peroxide  without  any  loss  of  activity. 

Bredig  (1899)  has  recently  enlarged  the  class  of  catalysers  by 
showing  that  all  metals  in  a  colloidal  state,  to  which  he  gives  the 
name  of  inorganic  ferments,  belong  to  it.  Moreover,  he  has 
brought  out  so  many  interesting  coincidences  between  the  action 
of  these  catalysers  and  that  of  enzymes  as  to  render  the  hypothesis 


32  PHYSIOLOGY  CHAP. 

highly  probable  that  both  classes  of  substances  act  in  virtue  of  the 
same  principle. 

To  Ostwald  is  due  the  special  distinction  of  having  effectively 
contributed  to  our  knowledge  of  the  mode  of  action  of  catalysers. 
According  to  him,  every  catalytic  process  consists  essentially  of  a 
change  of  velocity  in  a  chemical  process,  which  occurs  spontaneously. 
"  A  catalyser  is  a  body  which,  without  appearing  in  the  end  product 
of  a  chemical  reaction,  alters  its  velocity  by  accelerating  or  by 
retarding  it." 

This  theory  is  especially  applicable  to  the  example  cited  of 
hydrogen  peroxide  and  platinum  black  :  we  know,  in  fact,  that 
the  hydrogen  peroxide  slowly  decomposes  by  itself  into  water  and 
oxygen,  to  such  an  extent  that  after  a  few  days  there  is  no  longer 
any  trace  of  the  hydrogen  peroxide  in  an  open  vessel  containing 
it.  The  platinum  black  merely  accelerates  the  spontaneous 
process  of  scission.  The  same  thing  must  occur  in  the  case  of 
enzymes  and  the  substances  which  they  split  up. 

This  is  not  the  place  for  discussion  of  the  various  theories 
put  forward  to  explain  the  action  of  catalysers  and  of  fer- 
ments :  it  need  only  be  said  that  nowadays  everything  points  to 
the  conclusion  that  this  action  is  effected  not  directly,  but  by 
the  formation  of  intermediate  products  (which  do  no.t,  however, 
appear  in  the  end  products  of  cleavage),  and  that  according  to 
Euler  enzymes  and  catalysers  act  as  collectors  of  ions. 

X.  In  the  present  state  of  physiology  the  only  possible  basis 
for  a  classification  of  the  different  enzymes  is  the  changes  which 
they  effect. 

According  to  Hainmarsten,  the  enzymes  which  have  more 
especially  been  made  the  subject  of  experimental  research  may  be 
subdivided  into  two  great  classes,  i.e.  liydrolytic  and  oxidative. 

The  class  of  hydrolytic  ferments,  i.e.  those  which  split  up 
complex  chemical  aggregates  into  simpler  molecules  by  the 
absorption  of  molecules  of  water,  comprises  all  the  several  digestive 
ferments,  which,  as  we  shall  see,  fulfil  the  office  of  disintegrating 
complex  proteins,  polysaccharides  and  alimentary  fats  into  simpler 
compounds.  The  latter  are  better  adapted  for  absorption  by  the 
intestinal  epithelium,  where  they  are  either  finally  split  up,  or 
elaborated  into  new  and  more  complex  chemical  compounds  by  the 
metabolic  activity  of  the  tissues.  They  are  :— 

(a)  PrQteolytic  or  proteoclastic  enzymes,  which  split  up 
proteins,  and  of  which  we  have  already  spoken.  In  the  animal 
body  there  are  two  (according  to  some  authors,  three)  different 
types  of  proteolytic  ferments — pepsin,  trypsin,  and  to  these, 
according  to  some  modern  workers  (O.  Cohnheim),  erepsin  must  be 
added.  We  shall  deal  fully  with  these  enzymes  in  the  chapter  on 
Digestion.  Vegetable  proteolytic  ferments  (e.g.  papain)  are  also* 
known. 


i  LIVING  MATTEE  33 

(6)  Amy-olytic  enzymes  or  amylases,  which  split  the  poly- 
saccharides  (starch,  etc.)  into  di-  or  mono-saccharides.  To  these 
belong  the  various  diastases  of  the  animal  and  plant  kingdom 
(ptyalin,  aniylopsin).  The  so-called  invertases  which  split  di- 
saccharides  into  mono-saccharides  are  in  close  relation  with  these ; 
e.g.  maltase  which  splits  maltose  into  two  molecules  of  glucose ; 
invertase,  which  splits  saccharose  into  one  molecule  of  fructose  and 
one  of  glucose ;  lactase,  which  splits  lactose  into  one  molecule  of 
glucose  and  one  of  galactose. 

(c)  Lipolytic  enzymes  or  Upases,  which  split  neutral  fats  into 
their  components,  i.e.  glycerin  and  fatty  acids.  To  these  belongs 
the  so-called  steapsin  of  the  pancreatic  juice  to  which,  according 
to  -the  latest  investigations,  must  be  added  another  lipase,  formed 
by  the  gastric  mucosa. 

The  class  of  hydrolytic  ferments  further  includes  a  number  of 
other  ferments  recently  discovered  in  the  tissues  and  organs  of 
animals  and  plants,  such  as  arginase,  which  splits  arginine  into 
urea  and  ornithine ;  adenase  and  guanase,  which  split  up  adenine- 
and  guanine  respectively  into  ammonia  and  hypoxanthine  or 
xanthine ;  urease,  which  splits  urea  into  ammonia,  water,  carbonic 
acid,  etc. 

A  special  position  (which  has  been  little  noticed)  is  occupied 
by  the  so-called  coagulating  enzymes,  such  as  the  rennin  or 
chyrnosin  of  the  digestive  tube,  which  forms  casein  from  the 
caseinogen  of  milk,  and  thrombin  or  thrombase,  which  determines 
the  clotting  of  blood  by  transforming  fibrinogen  into  fibrin,  as  we 
shall  see  in  treating  of  blood  plasma. 

The  class  of  oxidising  ferments  contains  all  those  ferments 
which  determine  the  disintegration  of  complex  substances  by 
oxidising  them,  by  a  process  highly  similar  to  that  which  occurs  in 
inorganic  nature  in  the  various  forms  of  combustion,  e.g.  of  carbon, 
which  burns,  combining  with  the  oxygen  of  the  air. 

These  ferments,  too,  are  analytic,  i.e.  they  break  down  the 
complex  chemical  compounds  into  simpler  compounds,  making 
them  richer  in  oxygen  derived  from  the  atmosphere  or  other 
sources — and  thereby  liberating  a  certain  quantity  of  potential 
chemical  energy.  Great  importance  is  ascribed  to  these  oxidising 
ferments,  as  they  are  the  agents  of  the  various  processes  of  oxida- 
tion, which  occur,  as  we  shall  frequently  find,  within  the  living 
organism :  and  it  has  been  possible,  by  modern  methods  of  research, 
to  isolate  a  large  number  of  enzymes  belonging  to  this  class  from 
animal  and  vegetable  tissues. 

Direct  oxidases  (the  name  given  to  the  oxidising  ferments) 
must  be  distinguished  from  the  indirect,  which  are  known  as- 
peroxidases.  The  former  are  capable  of  causing  oxygen  to 
act  directly;  the  latter  can  only  oxidise  in  the  presence  of 
peroxides  (hydrogen  peroxide).  Oxidases  give  a  blue  reaction 
VOL.  i  D 


34  PHYSIOLOGY  CHAP. 

directly  with  tincture  of  guaiacum,  peroxidases  only  in  presence 
of  a  peroxide. 

Some  consider  as  a  third  group  of  the  oxidising  ferments  the 
so-called  catalases,  which  split  up  hydrogen  peroxide  into  oxygen 
and  water,  but  never  give  a  blue  reaction  with  tincture  of 
guaiacum. 

The  alcoholic  fermentation  of  glucose  by  means  of  beer  yeast, 
or  the  ferment  known  as  zymase,  which  was  first  isolated  by 
Buchner  from  the  cells  of  that  micro-organism,  is  not  a  true  and 
proper  oxidation  in  which  free  oxygen  is  absorbed  by  the  sugar — 
as  may  be  deduced  from  the  fact  that  such  fermentation  takes 
place  anaerobically,  and  according  to  the  equation  : — 

C0H12O6  =  2C,H5OH  +  200., 
Glucose          Alcohol      Carbonic 
acid 

It  should  rather  be  considered  as  an  internal  or  intra-niolecular 
oxidation,  by  which  part  of  the  molecule  of  glucose  is  oxidised, 
and  burns  at  the  expense  of  the  other  part,  till  it  finally  splits  up 
into  alcohol  and  carbonic  acid.  According  to  recent  investigation, 
we  have  here  the  co-operation  of  two  separate  and  distinct 
enzymes,  one  of  which,  lactolase,  or  lactacidase,  converts  sugar  into 
lactic  acid,  while  the  other,  zymase,  or  alcoholase,  splits  the  lactic 
acid  into  alcohol  and  carbonic  acid. 

According  to  some  authors  (whose  conclusions  have,  however, 
been  warmly  disputed),  a  similar  anaerobic  fermentative  process  of 
glycolysis  takes  place  in  animal  tissues. 

In  conclusion  we  must  mention  another  class  of  ferments,  of 
which  we  know  at  present  even  less  than  those  already  discussed 
— the  so-called  reducing  ferments,  reductases  or  hydrogenases. 

Another  classification  of  enzymes  is  based  upon  the  difference 
of  place  in  which  they  normally  occur.  Thus,  to  the  ferments 
known  as  extracellular  or  secretory,  because  normally  found  in  the 
liquids  secreted  by  the  various  glands  or  cells,  are  opposed  the 
intracellular  ferments  or  endo-enzymes,  which  are  found  within 
the  cell,  and  represent  the  chemical  agents  by  which  the  cells  are 
able  to  split  up  or  fabricate  the  several  chemical  components  of 
their  substance.  To  this  class  of  endo-enzymes  belong  Buchner's 
zymase,  many  of  the  oxidases,  and  also  a  series  of  hydrolytic, 
proteoclastic  enzymes,  which  according  to  Vernon  are  of  the  type 
of  O.  Cohnheim's  erepsin. 

To  these  intracellular  proteolytic  ferments  are  due  the 
phenomena  of  post-mortem  autodigestion  or  autolysis,  described 
for  the  first  time  by  Salkowski  (1900),  which  occurs  in  the  organs 
or  organic  fluids,  when  isolated  from  the  body,  and  kept  free  of 
bacterial  or  extraneous  enzymatic  contamination.  After  a  certain 
lapse  of  time  it  can  be  shown  that  protein  cleavage  has  taken 


i  LIVING  MATTER  35 

place  in  the  tissues  or  fluids,  accompanied  by  a  similar  cleavage  of 
fats  and  carbohydrates. 

The  phenomena  of  post-mortem  autolysis  have  been  the  subject 
of  numerous  recent  researches,  in  the  hope  of  throwing  some  light 
upon  intra  vitam,  intracellular,  fermentative  processes,  which 
we  must  assume  to  be  of  great  importance  in  the  metabolism  of 
the  tissues  and  of  the  living  cells.  The  results  so  far  obtained 
are  not,  however,  decisive  enough  to  serve  as  the  basis  of  any 
definite  conclusion. 

XL  The  proteins  of  living  matter  are  always  accompanied  by 
a  large  amount  of  simpler  substances,  nitrogenous  or  non- 
nitrogenous,  which  represent  products  of  decomposition  or  of 
retrogressive  changes  in  these  substances,  or  in  nutrient  substances 
from  outside,  which  have  been  more  or  less  elaborated  by  the 
activity  of  the  cell.  The  name  deutoplasm  has  been  given  to 
these  substances  as  a  whole,  that  of  cytoplasm  being  reserved  for 
the  living  substance  generically  known  as  protoplasm. 

The  nitrogenous  products  of  the  retrogressive  metamorphoses 
of  protein  form  a  series  of  well-defined  chemical  substances,  many 
of  which  are  eliminated  with  the  urine  in  very  varying  amounts 
in  the  higher  animals.  The  largest  in  quantity  and  in  nitrogen 
content  is  urea,  next  come  uric  acid,  hippuric  acid,  creatine  and 
creatinine.  The  purine  bases  form  a  distinct  group  already  referred 
to,  xanthine,  hypoxanthine  or  sarkine,  adenine,  guanine,  and  they 
are  the  decomposition  products  of  nuclein.  These  substances 
cannot  all  be  extracted  from  the  tissues,  owing  to  the  minimal 
quantity  in  which  they  are  present.  Another  group  of  nitrogenous 
and  phosphorised  substances,  the  lecithins,  occur,  according  to 
Hoppe-Seyler,  in  every  plant  and  animal  cell,  and  in  particularly 
large  quantities  in  the  elements  of  nerve,  the  blood  corpuscles  and 
in  yolk  of  egg.  In  its  chemical  characters  (solubility  in  ether  and 
alcohol,  insolubility  in  water)  lecithin  shows  great  similarity  to 
fats.  It  resembles  nuclein  inasmuch  as  it  contains  phosphorus, 
and  is  capable  of  forming  unstable  combinations  with  albumin  and 
other  substances.  The  yolk  of  egg  contains  a  combination  of 
lecithin  with  vitellin.  Protagon,  extracted  by  Liebreich  (1865)  from 
the  brain,  is  the  combination  of  a  lecithin  with  cerebrin,  a  nitrogen- 
ous substance  free  from  phosphorus,  similar  to  the  glucosides. 

The  non-nitrogenous  organic  products  which  enter  into  the 
chemical  constitution  of  the  cell  are  represented  by  the  fats  and 
carbohydrates.  These  originate  partly  in  the  consumption  of 
proteins,  partly  from  external  food-stuffs,  or  their  transformations 
as  effected  by  the  cell-enzymes. 

Chemically  considered,  the  fats  represent  combinations  of 
glycerin  (triatomic  alcohol)  with  the  acids  of  the  fatty  series 
(stearic,  palmitic,  butyric,  valerianic,  caproic),  as  also  with  oleic 
acid,  which  does  not  belong  to  the  normal  fatty  series. 


36  PHYSIOLOGY  CHAP. 

Cholesterin  resembles  the  fats  in  certain  of  its  characteristics, 
though  absolutely  unlike  them  in  its  chemical  constitution ;  it  is 
regularly  found  in  every  animal  and  plant  cell,  particularly  in  the 
brain  and  liver.  Since  it  is  a  secretion  from  the  skin  of  man  and 
other  animals,  it  is  found  in  the  epidermal  structures  (hair,  fur, 
feathers,  nails,  etc.),  for  which  it  forms  a  kind  of  protective  grease. 
Cholesterin  is  a  monatomic  alcohol  of  unknown  constitution,  which 
crystallises  from  alcoholic  solution  in  laminae  like  mother-of-pearl. 
Like  glycerin,  it  forms  with  fatty  acids  compounds  which  corre- 
spond to  the  fats. 

From  a  chemical  point  of  view  the  carbohydrates  are  aldehydic 
or  ketonic  derivatives  of  polyhydric  alcohols.  They  may  be  divided 
into  three  groups:  (a)  monosaccharides,  (V)  di-saccharides,  (c)  poly- 
saccharides. 

(a)  Among  the  monosaccharides  are  more  particularly  grape 
sugar  (glucose  or  dextrose)  and  fruit  sugar  (fructose  or  laevulose), 
which  are  abundant  in  plant  juices;  the  first  also  occurs  in  animal 
tissues.  They  turn  the  plane  of  polarised  light  to  the  right  or 
left.  They  are  readily  oxidised ;  they  are  fermented  by  yeast,  and 
converted  into  alcohol  and  carbonic  acid  : — 

C6H1206=2C2H5QH  +  2CO,,. 

They  have  the  property  of  readily  abstracting  oxygen  from  the 
surrounding  medium,  and  behave  as  reducing  agents  to  oxidised 
compounds.  This  property  is  utilised  in  detecting  the  presence  of 
sugars,  and  also  in  estimating  them.  The  tests  most  used  are 
Trommer's  and  Bottger's.  In  the  former  the  sugar  solution, 
rendered  alkaline  with  caustic  potash  or  soda,  on  adding  a  few  drops 
of  dilute  copper  sulphate,  and  heating,  reduces  the  copper  oxide 
to  cuprous  oxide,  a  suboxide  which  forms  a  reddish-yellow  pre- 
cipitate. In  the  second  test  a  few  drops  of  bismuth  subnitrate 
are  added  to  the  alkaline  solution  of  sugar,  which  is  turned  black 
by  the  reduction  of  the  bismuth  salt  to  the  metallic  state. 

Besides  these  two  tests,  which,  since  they  are  based  on  the 
reducing  property  of  glucose,  are  not,  strictly  speaking,  specific  to 
this  compound,  but  are  common  to  all  the  reducing  substances, 
three  other  specific  tests  are  known  for  glucose,  namely  Moore's 
test,  the  phenyl-hydrazine  test,  and  that  of  alcoholic  fermentation 
(biological  test). 

In  the  first  the  solution  of  glucose  is  warmed,  after  diluting  it 
with  about  a  quarter  of  its  volume  of  caustic  soda  or  potash.  The 
mixture  first  turns  yellow,  and  then  successively  (according  to  the 
content  of  sugar)  orange,  brown,  dark  brown,  giving  off  the  char- 
acteristic odour  of  burnt  sugar  or  caramel,  which  becomes  more 
intense  on  acidification. 

The  second  test  consists  in  warming  the  glucose  solution  with 


i  LIVING  MATTER  37 

acetate  of  phenyl-hydrazine  ;  characteristic  yellow  crystals  (needles) 
of  phenyl-glucosazone  are  formed  (E.  Fischer). 

The  biological  test  is  based  on  the  fact  that  beer  yeast  is  able 
to  provoke  alcoholic  fermentation  in  a  solution  of  glucose. 

We  shall  give  the  quantitative  tests  for  glucose  in  dealing 
with  urine. 

(6)  Di-saccharides  have  the  formula  C12H22OU,  which  represents 
the  combination  of  two  molecules  of  a  monosaccharide  with 
elimination  of  a  molecule  of  water.  The  most  important  are  cane 
sugar  (saccharose)  arid  milk  sugar  (lactose).  On  warming  with 
dilute  mineral  acids,  and  under  the  action  of  certain  bacteria,  the 
di-saccharides  are  inverted,  i.e.  transformed  into  monosaccharides. 
Under  the  fermentative  action  of  the  Bacterium  lacticum  these  last 
are  transformed  into  lactic  acid  (C6H1206  =  2C3H603).  With 
Bacillus  butyricus  lactic  acid  undergoes  further  decomposition, 
giving  rise  to  butyric  acid,  carbonic  acid,  and  hydrogen  :— 

2C3H003  =  C4H802  +  2C02  +  4H. 

(c)  Poly sacchar  ides  are  also  anhydrides  of  monosaccharides, 
and  result  from  the  combination  of  several  molecules ;  they  there- 
fore have  a  high  molecular  weight,  which  differs  in  different 
compounds  of  the  group.  Their  general  formula  is  wC6H1005. 
They  do  not  taste  sweet,  are  generally  amorphous,  are  partly 
soluble,  partly  insoluble  in  water,  and  are  convertible  into 
monosaccharides  by  various  means.  They  include  a  series  of 
bodies  widely  distributed  in  both  plant  and  animal  cells.  The 
most  important  are  starch,  which  in  the  form  of  stratified 
corpuscles  is  found  in  the  protoplasm  of  many  plant  cells ;  glycogen 
or  animal  starch,  which  occurs  in  almost  all  animal  tissues,  but 
particularly  in  the  amorphous  granules  of  the  hepatic  cells,  as  also 
in  muscle  fibre,  embryonic  tissue,  and  proliferating  cells  in  general ; 
animal  and  vegetable  gums;  cellulose,  which  is  the  principal 
component  of  the  cellular  membranes  of  plants,  and  is  also  found 
in  the  animal  kingdom  in  the  mantle  of  Tunicata  and  the 
chitinous  skeleton  of  insects. 

Polysaccharides  behave  variously  to  solutions  of  iodine.  The 
starches  turn  blue,  glycogen  brown  ;  cellulose  does  not  stain  at  all 
with  iodine,  and  only  assumes  a  bluish  tint  on  treatment  with 
sulphuric  acid. 

In  addition  to  free  carbohydrates,  living  protoplasm  contains 
other  compounds  such  as  mucin  and  chitin,  as  is  shown  in  their 
derivatives  and  decomposition  products  (dextrin,  sugar,  lactic  acid, 
butyric  acid,  etc.). 

The  inorganic  substance  of  elementary  organisms  consists  of 
water,  salts,  and  gases. 

Water  is  indispensable  to  the  activity  of  living  matter,  since 


38  PHYSIOLOGY  CHAP. 

it  dissolves  the  single  particles,  and  renders  them  capable  of  being 
transported.  It  is  present  partly  in  chemical  combination,  partly 
as  solvent  for  the  various  substances  of  the  cell-contents.  The 
amount  by  weight  of  water  in  the  tissues  is  on  an  average  over 
50  per  cent.  According  to  von  Bezold,  the  total  content  of  water 
in  the  human  body  is  about  59  per  cent.  Bone  contains  22  per 
cent  water,  liver  69  per  cent,  muscle  75  per  cent,  the  kidneys  82 
per  cent. 

The  water  holds  in  solution  a  number  of  salts,  which  are  never 
wanting  in  living  substance.  Chlorides  largely  predominate  ;  next 
come  the  carbonates,  sulphates,  phosphates  of  the  alkalies  and 
alkaline  earths.  Such  are  the  chlorides  of  sodium,  potassium,  and 
ammonium ;  the  carbonates,  sulphates,  and  phosphates  of  sodium, 
potassium,  calcium,  magnesium,  and  ammonium.  A  considerable 
part  of  these  salts  is  probably  in  chemical  combination  with  the 
organic  substances. 

The  gases,  oxygen,  carbonic  acid,  and  nitrogen,  when  not 
chemically  combined,  are  simply  dissolved  in  the  water ;  very 
occasionally  they  occur  in  the  form  of  gaseous  vesicles,  as  in 
certain  unicellular  Ehizopods. 

XII.  After  this  bird's-eye  review  of  the  vast  province  of  the 
chemistry  of  elementary  organisms,  undertaken  solely  with  the 
object  of  classifying  into  groups  and  subgroups  the  several  bodies 
that  compose  the  substratum  of  the  phenomena  of  life,  it  must 
again  be  emphasised  that  we  are  far  from  any  adequate  knowledge 
of  the  chemical  structure  of  living  matter.  It  is  impossible  to 
investigate  this  living  matter  without  first  killing  it,  i.e.  destroying 
its  vitality.  The  chemical  compounds,  organic  and  inorganic, 
which  we  have  seen  to  exist  in  plants  and  animals,  are  only  the 
products  of  this  destruction,  i.e.  they  represent  the  chemical 
aggregates,  which  can  be  recognised  and  isolated  from  the  dead 
body.  They  certainly  exist  in  the  cell ;  but  we  are  entirely 
ignorant  of  the  mode  in  which  they  are  associated  and  combined 
among  themselves,  so  as  to  compose  the  living  matter.  Nor 
should  this  surprise  us,  when  we  reflect  that  with  the  ordinary 
methods  of  chemical  analysis  we  have  no  means  of  ascertaining 
the  exact  chemical  nature  of  the  individual  salts  contained,  e.g.  in 
a  mineral  water.  We  can  only  determine  the  quality  and  quantity 
of  the  acids  and  bases  contained  in  it ;  as  to  what  these  salts  are, 
and  how  they  are  mixed  together,  we  know  nothing.  Any  state- 
ments in  regard  to  this  are  mere  guesswork. 

The  physiologist  needs  to  be  very  circumspect  and  cautious  in 
applying  the  data  thus  derived  from  the  chemistry  of  dead  matter 
to  the  phenomena  of  living  substance,  in  which  the  chemical 
relations  of  the  several  molecular  aggregates  are  very  different,  and 
the  molecules  themselves  are  highly  complex  and  excessively 
unstable. 


i  LIVING  MATTER  39 

Immense  progress  has  been  made  of  late  years  in  the  know- 
ledge of  the  finer  morphological  structure  of  the  cell,  which 
must  help  in  determining  the  chemical  differences  between  the 
protoplasm  and  the  nucleus,  respectively.  The  first  advances  in 
this  direction  are  due  to  the  methods  of  Micro-Chemistry. 

Kossel's  work  (1891)  has  shown  that  in  the  nucleus,  compounds 
of  protein  with  substances  containing  phosphorus  largely  pre- 
dominate, while  the  cytoplasm  consists  principally  of  simple 
proteins  and  their  compounds  with  combinations  which  contain 
no  phosphorus.  Miescher  had  previously  demonstrated  (1874) 
that  the  nucleins  which  he  discovered  resist  the  digestive  action  of 
gastric  juice,  and  that  on  placing  cells  of  various  kinds  in  this 
juice  the  cytoplasm  of  the  cell  dissolves,  while  the  nuclei  remain, 
although  of  smaller  size.  Malfatti  (1892)  next  showed  that  it  is 
the  chromatic  substance  and  the  nucleolus  of  the  nuclei  which  do  not 
digest,  while  the  nuclear  fluid  and  a-chromatic  substance  dissolve. 
This  proves  the  chromatic  substance  and  the  nucleolus  of  the  nuclei 
to  consist  essentially  of  nucleins  or  their  combinations,  while  the 
cell  protoplasm  consists  of  other  proteins.  Lastly,  Lilienfeld  and 
Monti  (1892)  showed  that  ammonium  molybdate  is  a  micro- 
chemical  reagent  for  phosphorus -containing  substances,  in  the 
presence  of  which  phospho-molybdic  acid  is  formed,  which  stains 
brown  on  the  addition  of  pyrogallol.  By  means  of  this  reagent 
it  has  been  ascertained  that  the  compounds  of  phosphorus,  in  the 
most  dissimilar  cells,  are  almost  exclusively  contained  in  the 
nucleus.1 

Carbohydrates  and  fats,  on  the  other  hand,  are  almost  ex- 
clusively localised  in  the  cytoplasm  and  limiting  cell  membrane. 

Nothing  is  known  in  regard  to  the  localisation  of  the  inorganic 
compounds;  except  that,  according  to  Yahlen,  potassium  compounds 
are  absent  from  the  nuclei  of  cells. 

BIBLIOGRAPHY 

F.  HOPPE-SEYLER.     Pliysiologische  Chenrie,  I.  Teil,  Allg.  Biol.     Berlin,  1877. 

0.  HERTWIG.  Die  Zelle  u.  die  Gewebe.  Jena,  1893-1898.  (English  translation, 
The  Cell,  Campbell,  1895.) 

M.  VERWORN.  Allgeraeine  Physiologic.  4th  ed.  Jena,  1906.  (English  transla- 
tion, General  Physiology,  by  F.  S.  Lee.  Macmillan,  1899.) 

R.  NEUMEISTER.     Lehrbuch  d.  physiologischen  Cheniie.     Jena,  2nd  ed.,  1892. 

F.  BOTTAZZI.     Trattato  di  chimica  fisiologica.     Milan,  1898. 

0.  HAMMARSTEN.  Lehrbuch  d.  physiologischen  Cheniie.  Wiesbaden,  6th  ed., 
1907. 

E.  ABDERHALDEN.  Lehrbuch  d.  physiologischen  Chemie.  Berlin  and  Vienna, 
1906. 

E.  FISCHER.  Untersuchungen  iiber  Aniino-sauren,  Polypeptide,  u.  Proteine. 
Berlin,  1896. 

1  Scott  has  shown  that  it  is  only  the  inorganic  phosphates  which  react  with 
this  reagent.  Organic  phosphorus  compounds  do  not  react,  especially  those  of  the 
nuclein  type,  which  are  not  readily  hydrolysed  into  phosphoric  acid.— PLIMMER  arid 
SCOTT. 


40  PHYSIOLOGY  CHAP. 

C.  OPPENHEIMER.     Die  Fermente  u.  ihre  Wirkungen.     Leipzig,  Vogel,  1903. 

O.  BIIEDIG.      Die   Elemeute    d.    chemischen    Kinetik,    mit    besonderer    Beriick- 

sichtigung  des  Katalyse  u.  der  Ferment- Wirkung.     Ergebnisse  d.  Physiol.,  I. 

Part  I.,  1901. 

Recent  English  literature  of  the  subject : — 

F.  G.  HOPKINS  and  S.   W.  COLE.     A  Contribution  to  the  Chemistry  of  Proteid^, 

Part  I.     Journ.  of  Physiol.,  1901-2,  xxvii.  418. 
P.    A.   LEVENE  and   L.    B.    MENDEL.      Some   Decomposition    Products    of   the 

Crystallized  Vegetable  Proteid  edestin.     Amer.  Journ.  of  Physiol.,  1902,  vi. 

48. 
A.  N.  RICHARDS  and  W.  J.  GIES.     Chemical  Studies  of  Elastin,  Mucoid,  and  other 

Proteids    in    Elastic    Tissue,    with    some   Notes   on    Ligament   Extractives. 

Amer.  Journ.  of  Physiol.,  1902,  vii.  93. 
W.  W.  LESEM  and  W.  J.  GIES.     Notes  on  the  Protagon  of  the  Brain.     Amer. 

Journ.  of  Physiol.,  1903,  viii.  183. 
F.  G.  HOPKINS  and  S.  W.  COLE.     A  Contribution  to  the  Chemistry  of  Proteids, 

Part  II.     Journ.  of  Physiol.,  1903,  xxix.  451. 
W.  CRAMER.     On  Protagon,  Cholin,  and  Neurin.     Journ.  of  Physiol.,  1904,  xxxi. 

30. 
C.    SEIFERT  and   \V.    J.    GIES.     On   the   Distribution   of  Osseo-mucoid.     Amer. 

Journ.  of  Physiol.,  1904,  x.  146. 
H.  NEILSON.     The  Hydrolysis  and  Synthesis  of  Fats  by  Platinum  Black.     Amer. 

Journ.  of  Physiol.,  1904,  x.  191. 
H.    G.   WELLS.     On  the  Relation  of  Autolysis   to   Proteid  Metabolism.     Amer. 

Journ.  of  Physiol.,  1904,  xi.  351. 
E.  R.  POSNEII.     Do  the  Mucoids  combine  with  other  Proteids  ?    Amer.  Journ.  of 

Physiol.,  1904,  xi.  404. 
P.  A.   LEVENE.     The  Autolysis  of  Animal  Organs.     Amer.  Journ.  of  Physiol., 

1904,  xi.  437  and  xii.  276. 
T.  B.  OSBORNE  and  I.  F.  HARRIS.      The  Precipitation  Limits  with  Ammonium 

Sulphate  of  some  Vegetable  Proteins.     Amer.  Journ.   of  Physiol.,  1905,  xiii. 

436. 
T.  B.  OSBORNE  and  I.  F.  HARRIS.     The  Solubility  of  Globulin  in  Salt  Solution. 

Amer.  Journ.  of  Physiol.,  1905,  xiv.  151. 
H.  C.  HASLAM.     The  Separation  of  Proteids.     Journ.  of  Physiol.,  1905,  xxxii. 

267. 
R.  H.  A.  PLIMMKR.     The  Formation  of  Prussic  Acid  by  the  Oxidation  of  Albumins. 

Journ.  of  Physiol.,  1904,  xxxi.  65  ;  and  1905,  xxxii.  51. 
P.  A.  LEVENE.     The  Cleavage  Products  of  Proteoses.     Journ.  of  Biolog.  Chem., 

1905-6,  i.  45. 

E.  R.  POSNER  and  W.  J.  GIES.     Is  Protagon  a  Mechanical  Mixture  of  Substances, 

or  a  definite  Chemical  Compound  ?    Journ.  of  Biolog.  Chem.,  1905-6,  i.  59. 
H.  D.  DAKIN.     The  Oxidation  of  Amido-acids  with  the  Production  of  Substances 

of  Biological  Importance.     Journ.  of  Biolog.  Chem.,  1905-6,  i.  171. 
A.  E.  TAYLOR.     On   the  Synthesis  of  Protein   through   the   Action  of  Trypsin. 

Journ.  of  Biolog.  Chem.,  1907,  iii.  87. 
T.   B.  ROBERTSON.     Note  on  the   Synthesis   of  Protein   through   the  Action  of 

Trypsin.     Journ.  of  Biolog.  Chem.,  1907,  iii.  87. 
C.  H.  NEILSON.     Further   Evidence   on   the   Similarity  between  Catalysis   and 

Enzyme  Action.     Amer.  Journ.  of  Physiol.,  1905-6,  xv.  148. 
C.  H.  NEILSON.     The  Inversion  of  Starcli  by  Platinum  Black.      Amer.  Journ. 

of  Physiol.,  1905-6,  xv.  412. 
W.  B.  HARDY.     Colloidal  Solution.     The  Globulins.     Journ.  of  Physiol.,  1905-6, 

xxxiii.  251. 
R.   H.  A.  PLIMMER  and  W.   M.  BAYLISS.     The  Separation  of  Phosphorus  from 

Caseinogen  by  the  Action  of  Enzymes  and  Alkali.     Journ.  of  Physiol.,  1905-6, 

xxxiii.  439. 

F.  G.  HOPKINS  and  E.  G.  WILLCOCK.     The  Importance  of  Individual  Amino-acids 

in  Metabolism.     Journ.  of  Physiol.,  1906-7,  xxxv.  88. 

W.  M.  BAYLISS.     Researches  on  the  Nature  of  Enzyme  Action.     Journ.  of  Physio  ., 
1907-8,  xxxvi.  221. 


j  LIVING  MATTEK  41 

W.  M.  BAYLISS.     The  Nature  of  Enzyme  Action.     London,  1908. 

P.   HARTLEY.     On  the  Nature  of  the  Fat  contained  in  the  Liver,   Kidney,   and 

Heart.     Journ.  of  Physiol.,  1907-8,  xxxvi.  17. 
O.  ROSENHEIM  and  M.  C.  TEBB.     The  Non-existence  of  "  Protagon  "  as  a  definite 

Chemical  Compound.     Journ.  of  Physiol,  1907-8,  xxxvi.  1. 
H.  D.  DARIN.     Comparative  Studies  of  the  Mode  of  Oxidation  of  Phenyl  Derivatives 

of  Fatty  Acids  by  the  Animal  Organism  and  by  Hydrogen  Peroxide.     Journ. 

of  Biolog.  Chem.,  1908,  iv.  419  ;  and  1908-9,  v.  173,  303. 
R.  H.  A.  PLIMMER  and  F.   H.  SCOTT.     The  Distribution  of  Phospho-proteins  in 

Tissues.     Trans.  Chem.  Soc.,  1908,  xciii.  1699. 
A.   E.  TAYLOR.     On  the  Synthesis  of  Protamin  through  Ferment  Action.     Journ. 

of  Biolog.  Chem.,  1908-9,  v.  381. 
A.    E.  TAYLOR.     On  the  Composition  and   Derivation  of  Protamin.      Journ.    of 

Biolog.  Chem.,  1908-9,  v.  389. 
T.    B.    ROBERTSON.     On   the    Synthesis   of  Paranuclein   through   the  Agency   of 

.Pepsin,  etc.,  etc.     Journ.  of  Biolog.  Chem.,  1908-9,  v.  493. 
R.  H.  A.  PLEMMER  and  F.  H.  SCOTT.     The  Transformations  in  the  Phosphorus 

Compounds  in  the  Hen's  Egg  during  Development.     Journ.  of  Physiol.,  1909, 

xxxviii.  247. 
T.     B.     OSBORNE,    LEAVENWORTH   and   BRAUTLECHT.     The   Different  Forms   of 

Nitrogen  in  Proteins.     Amer.  Journ.  of  Physiol.,  1908-9,  xxiii.  180. 
R.    H.    A.    PLIMMER  and   R.    KAYA.      The  Distribution  of  Phospho-proteins  in 

Tissues,  Part  II.     Journ.  of  Physiol.,  1909-10,  xxxix.  45. 
E.   V.   McCoLLUM.     Nuclein  Synthesis  in   the   Animal  Body.     Amer.    Journ.    of 

Physiol.,  1909-10,  xxv.  120. 


CHAPTEK    II 

LIVING  MATTER:  ITS  FUNDAMENTAL  PROPERTIES 

CONTENTS. — Vital  metabolism  and  phenomena  of  nutrition  and  reproduction. 
2.  Vital  metabolism  and  phenomena  of  excitability  and  sensibility.  3.  Laws  of 
stability  and  variability  of  living  species.  Critical  examination  of  Theory  of 
Evolution  ;  Darwinism,  and  Neo-Lamarckism.  4.  Evolutionary  theories  of  Nageli, 
Weismann,  De  Vries.  5.  Distinctive  characters  of  plants  and  animals  :  (a}  Doc- 
trine of  Linnaeus  ;  (b)  doctrine  of  Cuvier  ;  (c)  doctrine  of  J.  R.  Mayer,  Dumas, 
Liebig.  6.  Different  forms  of  plant  and  animal  metabolism :  (a)  Nitrifying 
bacteria  ;  (6)  green  plants  ;  (c)  a-chlorophyllous  plants  ;  (d)  herbivorous  and 
carnivorous  plants.  Bibliography. 

THE  fine  morphological  organisation  and  highly  complex  chemico- 
physical  structure  of  elementary  organisms,  while  sufficiently 
distinctive  in  character  to  differentiate  non-living  matter  from 
living  bodies,  are  not  adequate  to  distinguish  the  living  body  from 
the  dead,  or  from  the  products  elaborated  by  the  living.  As  a 
matter  of  fact,  our  knowledge  of  cytological  structure  depends 
mainly,  and  the  data  we  possess  in  regard  to  the  chemical  composi- 
tion of  the  cell  depend  entirely,  upon  observations  made  on  the 
dead  organism. 

Yet  it  is  upon  the  cytological  and  physico-chemical  structure 
of  the  cell  that  the  physiological  activity  and  functions  common 
to  all  living  beings  are  founded,  and  it  is  by  these  that  they  are 
characteristically  distinguished  from  non-living  matter. 

General  Physiology  has  of  late  undergone  a  remarkable 
development  in  the  direction  of  philosophical  interpretation.  We 
must  here  confine  ourselves  to  summarising  the  most  definitely 
ascertained  conclusions — passing  over  the  many  hypotheses  by 
which  it  is  attempted  to  fill  the  unbridged  gaps,  and  keeping 
strictly  to  what  may  serve  as  the  foundation  of  scientific  culture, 
and  preparation  to  the  study  of  human  physiology. 

I.  Life  is  essentially  characterised  by  instability  and  movement, 
by  the  constant  transformation  of  matter,  with  a  corresponding 
evolution  and  accumulation  of  energy,  which  is  exhibited  in  uni- 
cellular as  in  multicellular  organisms,  in  plants  as  in  animals. 
The  name  Metabolism  (/zcra/^oA.?/,  change)  has  been  given  to  these 
physico-chemical  changes  of  living  protoplasm  as  a  whole.  It  is 

42 


CHAP,  ii  LIVING  MATTER  43 

the  result  of  two  opposite  processes,  which  are  continually  super- 
posed and  succeed  each  other  :  a  synthetic,  assimilative,  and  con- 
structive process,  known  as  anabolism,  and  an  analytical,  dissimila- 
tive,  and  destructive  process,  known  as  katabolism. 

In  the  anabolic  process,  the  cell  forms  or  elaborates  organic 
matter  from  the  nutrient  materials,  by  the  aid  of  energies  derived 
from  the  environment  or  developed  by  oxidation  of  its  own 
substance  ;  it  takes  up  this  organic  matter  by  intussusception, 
transforms  it  into  living  protoplasm,  or  stores  it  as  reserve 
material. 

In  the  katabolic  process,  the  cell  breaks  up  and  uses  the 
reserve  materials,  disintegrates  its  own  protoplasm,  and  returns 
to  the  environment  the  products  of  decomposition,  combustion, 
and  activity. 

While  the  two  opposite  processes  which  constitute  metabolism, 
or  the  exchanges  of  matter  and  energy,  are  intimately  connected, 
they  are  differently  distributed  in  the  two  principal  phases  of  life, 
the  progressive  and  the  retrogressive.  During  the  first  phase  the 
organism  grows  and  develops,  and  is  active  in  its  functions; 
during  the  second,  it  dwindles  and  degenerates,  and  its  functions 
are  abated.  The  characteristic  phenomena  of  nutrition,  growth, 
and  development  in  the  organism  are  the  natural  consequences  of 
metabolism,  where  the  assirnilatory  or  anabolic  processes  prepon- 
derate ;  so,  too,  atrophy,  senility,  and  death  result  from  predomin- 
ance of  the  dissimilatory  or  katabolic  processes,  when  life  is  on  the 
wane. 

Between  the  progressive  and  retrogressive  phases  of  life, 
between  youth  and  age,  there  lies  a  long  intermediate  period, 
during  which  the  two  opposite  processes,  anabolic  and  katabolic, 
are  practically  in  equilibrium.  This  is  the  phase  of  maturity, 
characterised  by  the  full  and  vigorous  exercise  of  all  the  vital 
functions,  more  particularly  of  the  reproductive  capacity. 

It  is  only  when  growth  and  ontogenic  development  are  com- 
plete that  the  organism  is  able  to  reproduce  itself.  In  other  words, 
only  when  the  factors  or  hereditary  tendencies  accumulated  within 
the  germ  from  which  the  organism  has  arisen,  have  become  per- 
fectly developed  and  active,  is  it  capable  of  forming  by  itself  or 
by  intercourse  with  an  individual  of  the  opposite  sex,  new  germs, 
i.e.  new  aggregates  of  hereditary  elements  adapted  for  reproduction 
and  conservation  of  the  species. 

Metabolism  is  the  invariable  physiological  basis  of  these 
marvellous  phenomena :  when  the  anabolic  process  predominates, 
the  hereditary  tendencies  contained  in  the  germ  develop  and 
become  active;  when  the  evolution  of  the  individual  is  com- 
plete, the  metabolic  process  is  turned  to  preparing  the  hereditary 
material  of  new  organisms. 

II.  Metabolism  as  the  exchange  of  matter  between  organism 


44  PHYSIOLOGY  CHAP. 

and  environment  is  intimately  connected  with  metabolism  as 
exchange  of  energy.  Each  living  organism  contains  within  itself 
at  any  given  moment  of  its  life  a  sum  of  potential  energy,  drawn 
from  the  sun's  rays,  and  from  the  food-stuffs  which  it  has  ac- 
cumulated or  assimilated ;  and  this  energy  is  always  ready  to 
discharge  itself,  or  explode  by  transformation  into  kinetic  energy, 
in  consequence  either  of  internal  impulses  or  of  external  stimuli. 
The  most  striking  form  assumed  by  the  energy  developed  in  a 
living  organism  is  the  movement  of  masses,  the  power  of  surmount- 
ing resistance,  i.e.  of  doing  mechanical  work.  When  these  move- 
ments or  changes  of  form  or  position  in  space  depend  upon  internal 
stimuli  they  appear  to  be  spontaneous  or  automatic,  and  are  the 
most  common  and  obvious  objective  sign  that  the  organism  that 
accomplishes  them  is  living.  When  they  are  provoked  by  external 
stimuli  they  appear  as  reflex  movements,  i.e.  as  the  effects  of 
internal  reactions  to  external  stimuli ;  in  that  case  there  is  a 
striking  disproportion  between  action  and  reaction,  although  this . 
is  not  a  distinctive  sign  of  life,  since  the  same  may  be  observed  in 
many  chemical  combinations — the  so-called  explosives.  What 
does,  however,  differentiate  the  latter  from  living  substances,  is 
that  the  chemical  activity  of  explosives  exhausts  itself  in  the 
explosion,  while  the  organism  becomes  fatigued  with  work,  and 
recuperates  in  repose,  i.e.  at  each  reaction  it  only  discharges  part 
of  its  energy,  and  during  the  functional  pauses  it  recovers  by  the 
-anabolic  process  the  quantity  of  potential  energy  that  has  been 
consumed. 

This  peculiar  capacity  for  developing,  spending,  and  reaccum- 
ulating  energy,  which  characterises  living  beings,  has  received 
the  name  of  Excitability,  and  is  distinguished  as  reflex  or  auto- 
matic, according  as  the  reactions  or  excitations  are  provoked  by 
internal  tendencies  or  impulses,  or  by  external  stimuli,  or  excita- 
tions extrinsic  to  the  organism. 

That  there  must  be  a  marked  analogy  between  the  internal 
conditions  of  automatic,  and  those  of  reflex  excitability,  appears 
from  the  fact  that  it  is  often  very  difficult  to  differentiate  objec- 
tively between  automatic  movements  and  reflexes;  on  the  other 
hand,  many  movements  originally  automatic  become  reflex  by 
a  simple  morphological  evolution  of  the  elementary  organism 
that  produces  them,  while  many  originally  reflex  movements 
become  automatic  by  long  exercise  and  habit. 

These  phenomena  of  excitability,  which  can  be  observed  under 
various  forms  in  all  living  organisms,  are  intimately  connected 
with  another  group  of  phenomena,  that  can  be  directly  observed 
upon  ourselves  alone,  since  they  are  accessible  only  to  immediate 
internal  observation  or  introspection.  These  last  are  the  psychical 
phenomena,  which  as  a  whole  constitute  the  content  of  con- 
sciousness. 


ii  LIVING  MATTER  45- 

The  most  rudimentary  forms  of  consciousness,  and  as  such  the 
most  widely  dispersed  (common,  it  may  be,  to  all  living  beings),  are 
represented  by  the  phenomena  of  Sensibility,  taken  in  the  true 
psychological  and  not  in  the  metaphorical  sense — which  is  invari- 
ably intended  by  physicists  in  speaking,  e.g.  of  the  sensibility  of 
the  balance,  galvanometer,  or  thermopile. 

Certain  physiologists,  including  Claude  Bernard,  have  con- 
sidered sensibility  to  be  the  highest  form,  or  evolutionary  product, 
of  excitability,  i.e.  of  the  physiological  property  common  to  all, 
even  elementary,  organisms  of  reacting  to  stimuli  according  to- 
their  nature.  This,  however,  is  either  to  disallow  the  psychical 
import  of  the  word  sensibility,  or  to  admit  as  a  fact  that  which  is 
wholly  inconceivable,  i.e.  the  emergence  of  any  psychical  pheno- 
menon— even  in  the  form  of  vague  internal  sensations — from 
simple  molecular  movements.  According  to  our  physiological 
concepts,  sensibility  and  excitability  do  but  express  the  same  thing 
from  two  different  standpoints.  "  Excitability  is  for  us  sensibility 
expressed  in  a  verbal  symbol  suggested  by  external  observation  ; 
sensibility  is  the  same  excitability  expressed  in  a  verbal  symbol 
derived  from  introspection.  If  we  denote  by  excitation  and 
sensation  the  effects  corresponding,  respectively,  to  excitability  and 
sensibility,  then  excitation  is  the  objective  or  material  aspect 
of  sensation  ;  sensation  is  the  subjective  or  psychical  aspect  of 
excitation  "  (Luciani,  1892). 

This  is  merely  a  formal  statement  of  the  fundamental  hypo- 
thesis of  psychophysics,  viz.  that  psychical  phenomena  are  the 
correlatives  of  physiological  phenomena,  and  express  the  aspects- 
under  which  the  latter  surge  up  in  consciousness,  and  form  its 
content.  From  the  objective  standpoint,  psychical  phenomena 
also  must  be  regarded  as  so  many  forms  of  excitation,  determined 
by  the  metabolism  of  the  protoplasm,  which  is  the  common  physio- 
logical basis  of  all  vital  phenomena. 

III.  In  fulfilling  the  functions  of  nutrition,  reproduction, 
excitability,  and  sensibility,  all  plant  and  animal  organisms  are 
subject  to  two  laws,  which  to  a  certain  extent  are  antagonistic,  the 
Law  of  Heredity,  and  the  Law  of  Variation.  The  first  represents 
the  principle  of  Stability,  the  second  the  principle  of  Evolution. 
Neither  the  one  nor  the  other  are  to  be  understood  in  an  absolute 
sense,  since  they  are  mutually  exclusive,  but  it  is  extremely 
difficult  to  fix  the  precise  limit  between  stability  and  variability, 
as  appears  from  the  history  of  biological  science. 

Until  some  half-century  ago  the  mind  of  most  naturalists 
was  dominated  by  the  law  of  stability,  Fixity  of  Species  being 
a  dogma,  solemnly  proclaimed  by  Linnaeus  in  his  famous 
aphorism  "  Species  tot  sunt  quot  diversas  formas  ab  initio  produxit 
infinitum  Ens"  (Philosophia  botanica,  1751). 

A  little  more  than  a  century  later,  in  1859,  the  publication  of 


46  PHYSIOLOGY  CHAP. 

Darwin's  book  On  the  Origin  of  Species  by  Means  of  Natural 
Selection  caused  a  radical  change  in  the  ideas  of  the  naturalists, 
and  led  to  the  almost  unconditional  triumph  of  the  law  of  evolu- 
tion, to  the  detriment  of  the  law  of  stability.  The  evolutionists 
fell  into  excesses,  even  denying  the  existence  of  biological  species. 
We  have  recently  entered  upon  a  period  of  acute  criticism  of  old 
And  new  theories  of  the  Origin  of  Species,  and  at  present  the  con- 
viction is  gaining  ground  that  none  of  these  theories  has  an 
absolute  demonstrative  value,  all  having  rather  the  significance  of 
hypotheses  that  are  of  great  use  to  the  biologist  in  orientating 
himself  in  his  positive  researches. 

The  idea  of  evolution  has  till  now  been  the  only  conception 
imagined  by  the  naturalists  to  account  for  the  evident  affinity 
exhibited  among  themselves  by  the  different  plants  and  animals 
which  are  grouped  into  species,  genera,  families,  orders,  classes. 
In  all  these  groups  a  certain  conformity  of  morphological  type  is 
apparent. 

According  to  the  Evolutionary  Theory,  this  unity  of  type  is 
the  expression  of  a  unity  of  origin  (monophyletic  origin),  from 
which  the  various  families,  genera,  and  species,  animal  and  veget- 
able, have  been  derived  by  successive  differentiations.  Compara- 
tive anatomy,  embryology,  palaeontolog'y,  botanical  and  zoological 
geography,  offer  numerous  facts  that  accord  perfectly  with  the 
theory  of  evolution.  With  the  progress  of  biological  science, 
however,  other  data  have  gradually  emerged  that  are  difficult  to 
reconcile  with  the  concept  of  simple,  continuous,  monophyletic 
evolution. 

Many  of  the  resemblances,  analogies,  and  hornologies  admitted 
by  comparative  anatomists  up  to  a  few  years  ago  are  no  longer 
valid  in  face  of  a  more  profound  and  exact  knowledge  of  the  true 
structure  and  function  of  certain  organs  that  were  previously 
imperfectly  known.  For  embryologists,  the  value  of  the  so-called 
"  great  biogenic  law  "  that  was  held  by  certain  naturalists  to  be 
one  of  the  fundamental  proofs  of  evolution,  has  depreciated  owing 
to  the  many  exceptions  which  it  presents.  Further,  the  analogy 
between  the  development  of  the  individual  (ontogenesis)  and  the 
development  of  the  species  (phylogenesis)  is  essentially  different, 
since  the  cell-ovum  from  which  the  individuals  of  the  evolved 
species  originate  differs  entirely  from  the  ovum  of  the  Protista,  and 
must  in  itself  (by  a  still  incomprehensible  mystery)  contain  the 
whole  of  the  determinants  of  the  complex  final  development, 
determinants  that  are  obviously  wanting  in  the  ovum  of  Protista, 
or  are  contained  there  in  a  far  less  degree. 

Nor,  again,  have  recent  palaeontological  data  provided  all  the 
arguments  in  favour  of  the  theory  of  evolution  that  were  claimed  • 
a  few  years  ago.     Nowadays  we  can  no  longer  invoke  insufficiency 
of  material  to  explain  the  great  lacunae  found  in  the  development 


ii  LIVING  MATTEE  47 

of  fossil  plants  or  animals.  Species,  genera,  families  are  seen  to 
disappear  incontinently,  and  other  species,  other  genera,  other 
families  are  substituted  for  them,  with  no  evidence  of  that 
continuity  and  regularity  of  development  which  is  demanded  by 
the  theory  of  evolution.  Even  when  continuity  of  development 
is  observed  for  any  given  organ  (e.g.  the  foot  of  Solidungula),  it  is 
more  apparent  than  real,  since  it  has  been  arrived  at  by  observing 
a  single  organ  apart  from  all  the  other  organs  which  constitute 
the  species  under  consideration. 

Finally,  it  should  not  be  forgotten  that  the  fundamental 
basis  for  a  complete  and  satisfactory  theory  of  the  evolution  of 
the  entire  organic  world,  in  virtue  merely  of  the  elements  and 
forces  of  the  inorganic  world  (as  the  pure  evolutionists  maintain 
with  Spencer),  is  still  wanting,  viz.  the  demonstration  of  the 
spontaneous  generation  of  life  from  inorganic  matter  and  force. 
The  greater  the  progress  made  by  science,  the  more  do  the 
organisms  believed  to  be  simple  appear  complex,  and  the  more 
improbable  is  spontaneous  generation. 

Notwithstanding  this  and  other  serious  difficulties,  it  must  be 
admitted  that  the  hypothesis  of  evolution  has  proved  in  practice 
to  be  a  tool  of  remarkable  utility.  It  has  enabled  us  to  gather 
up  under  one  concept  an  infinite  variety  of  scattered  facts  which 
would  otherwise  have  escaped  the  researches  and  analysis  of 
modern  science,  and  thanks  to  which  our  positive  knowledge  has 
made  extraordinary  progress. 

Even  if  all  biologists  agree  in  admitting  the  theory  of  Evolu- 
tion, this  harmony  ceases  when  we  attempt  to  determine  its 
mechanism,  i.e.  its  real  causes  and  factors. 

The  Darwinians  and  the  so-called  neo-Darwinians  consider 
natural  selection  to  be  the  principal,  if  not  the  sole  factor  in 
evolution,  while  the  Lamarckians  and  the  neo-Lamarckians  almost 
entirely  deny  the  value  of  selection,  and  assert  on  the  contrary 
that  transformation  of  species  is  the  result  of  direct  adaptation  to 
the  variable  conditions  of  environment. 

Darwin  and  all  his  modern  followers,  while  they  defend  the 
principle  of  selection  to  the  hilt,  are  forced  to  admit  an  innate 
tendency  to  variation  within  the  species,  without  being  able  to 
indicate  its  causes.  If  the  said  variation  is  slow,  continuous, 
gradual  and  indefinite,  as  supposed  by  Darwin,  this  does  not 
explain  how  the  appearance  of  a  variation  can  turn  to  the  advan- 
tage of  the  species,  and  give  opportunity  for  selection,  in  such 
a  way  as  to  favour  the  individual  or  individuals  in  which  the  new 
variation  originates,  in  the  struggle  for  existence,  to  the  prejudice 
of  the  other  individuals  deprived  of  the  same  minimal  variation. 

On  the  other  hand,  the  concept  of  variability  of  species,  both 
in  plants  and  animals,  has  made  considerable  progress.  In  the 
time  of  Darwin  a  pure  speculation,  it  is  now  a  positive  experi- 


48  PHYSIOLOGY  CHAP. 

mental  fact ;  and  the  new  biometric  methods  have  led  to  the 
discovery  of  facts  and  laws  of  capital  importance  which  throw 
fresh  light  on  the  problem  of  the  origin  of  species,  showing  it  to 
be  far  more  complex  and  difficult  than  had  been  supposed. 

These  laws  demonstrate  the  necessity  of  carefully  distinguishing 
between  variation  and  variation. 

Some  variations  are  merely  quantitative  and  fluctuating,  and 
when  studied  by  the  statistical  method  are  found  to  be  subject  to 
the  so-called  Law  of  Quetelet.  Such  variations  are  in  strict 
relation  with  the  nutritive  conditions,  or  with  the  environmental 
conditions  in  general,  and  when  these  change,  the  values  of  the 
said  variations  change  also,  since  they  are  not  in  themselves 
hereditary ;  but  the  individuals  that  exhibit  them  return  to  the 
normal  type  whenever  the  conditions  of  the  environment  again 
become  normal.  It  is  clear  that  such  variations  can  have  no 
importance  in  determining  a  transmutation  of  species. 

Other  variations,  on  the  contrary,  are  qualitative  and  non- 
nuctuating,  and  are  not  subject  to  the  Law  of  Quetelet.  They  are 
fixed,  independent  of  the  condition  of  the  environment,  and  should 
in  reality  be  termed  not  variations,  but  typical  hereditary  forms, 
or  again  elementary  species  (or  races).  Each  of  the  classical 
Linnaean  species  comprises  a  greater  T)r  less  number  of  such  ele- 
mentary species,  which  in  the  first  instance  were  confused  with 
the  fundamental  typical  species,  and  were  erroneously  held  to 
be  simple  variations  of  the  same.  The  majority  of  our  plants 
and  domestic  animals  are  examples  of  these  elementary  species. 
Selection,  as  practised  artificially  by  man,  or  effected  by  Nature 
in  the  struggle  for  existence,  is  of  great  importance  in  the  sifting 
of  such  elementary  species  as  are  more  suited  to  the  needs 
of  man,  or  better  adapted  to  the  environmental  conditions.  It 
would,  however,  be  a  great  mistake  to  think  that  these  elementary 
species  were  created  and  formed  by  means  of  selection.  In  reality 
selection  did  nothing  more  than  seal  and  set  in  evidence  what 
already  existed  in  a  mixed  and  confused  state  in  the  fundamental 
species,  and  it  created  nothing  new.  Hence  the  majority  of  the 
examples  cited  by  Darwin  from  .plants  and  domestic  animals  are 
of  no  value  as  evidence  of  the  agency  of  selection  in  the  formation 
of  new  species.  It  is  on  this  account  that  many  speak  to-day  of 
a  crisis  in  Darwinism,  when  this  means  the  theory  of  selection 
in  a  restricted  sense,  and  is  not  a  synonym  of  evolution. 

The  falling-off  in  the  supporters  of  Darwinism  (in  this  limited 
sense)  has  reinforced  the  adherents  of  Lamarckism,  who  attribute 
the  origin  of  species  directly  to  the  environment,  to  the  action 
of  external  causes,  climate,  soil,  nutrition,  etc.  According  to 
Lamarck's  original  idea  (1809),  it  is  the  want  that  creates  the 
organ,  which  then  becomes  gradually  perfected  by  use,  while  with 
disuse  the  organ  atrophies  and  disappears.  This  idea  presupposes 


ii  LIVING  MATTER  49 

a  teleological  principle,  regulating  the  transmutation  and  adapt- 
ability of  the  new  organ,  a  principle  in  sharp  contrast  with  the 
canons  of  the  materialistic  doctrine,  which  seeks  for  the  mechanical 
causes  of  phenomena,  and  excludes  all  mystical,  transcendental 
interpretations.  The  neo-Larnarckians  renounce  the  teleological 
principle,  on  the  strength  of  recently  acquired  data  as  to  the 
determining  action  of  certain  external  agents,  e.g.  light,  heat, 
water,  gravity,  chemical  substances,  action  of  parasites,  mechanical 
action  (photomorphosis,  thermomorphosis,  hydromorphosis,  geornor- 
phosis,  chemomorphosis,  biomorphosis,  mechanomorphosis,  etc.). 
This  field  of  research,  as  cultivated  especially  by  the  modern 
botanist,  is  one  of  the  most  fruitful  to  the  progress  of  biological 
science. 

At  the  same  time  it  must  be  remembered  that  the  external 
agent,  e.g.  light  or  heat,  which  determines  a  modification  in 
the  structure  and  conformation  of  an  organ,  is  not  the  true  cause 
of  such  a  modification,  but  is  rather  the  external  stimulus  adapted 
to  develop  a  variation  which  already  existed  potentially  in  that 
organ.  The  determining  agent,  therefore,  creates  nothing  new,  it 
only  stimulates  the  species  to  the  expression  of  those  properties 
which  it  already  possesses  potentially.  This  conclusion,  which  is 
inevitable  in  the  present  state  of  our  knowledge,  must  obviously 
limit  to  a  great  extent  (some  even  say  reduce  to  zero)  the  value  of 
the  direct  action  of  external  agents  in  the  formation  and  trans- 
formation of  species. 

But  further :  in  order  that  the  influence  of  the  environment  in 
the  production  of  new  characters  in  a  species  shall  be  efficacious 
and  enduring,  it  is  necessary  to  presuppose  that  the  newly  acquired 
characters  are  hereditary.  Does  any  such  heredity  really  exist  ? 

This  is  one  of  the  problems  most  keenly  discussed  among 
modern  biologists.  It  is  obvious  that  a  decidedly  negative  reply 
would  cause  the  whole  edifice  of  the  Lamarckitrin  and  neo- 
Lamarckian  theory  to  crumble.  But  no  one  is  yet  in  a  position 
to  give  a  definite  answer.  The  majority  of  the  facts  that  were  at 
one  time  cited  in  proof  of  the  heredity  of  acquired  characters  have 
been  triumphantly  refuted  by  Weismann.  Some  few  data  relating 
to  the  lower  organisms  (Bacteria  and  Saccharomyces)  remain,  in 
which  the  heredity  of  newly  acquired  characters  seems  to  be  de- 
monstrated ;  but  how  far  these  data  are  of  value  in  the  solution 
of  the  general  problem  with  which  modern  biologists  are  so- 
engrossed,  is  a  matter  for  discussion. 

For  the  present  it  must  be  confessed  that  with  the  exception  of 
these  few  cases  among  the  inferior  organisms,  all  the  attempts 
hitherto  made  to  obtain  new  forms  of  plants  and  animals  by  the 
effect  of  one  or  several  external  causes  have  given  negative  results. 

IV.  Starting  from  a  profound  criticism  of  Darwinism  and 
Lamarckism,  Nageli  (1881?)  founded  a  new  theory  of  evolution,, 

VOL.  I  K 


50  PHYSIOLOGY  CHAP. 

according  to  which  the  origin  of  species  depends  upon  the  intimate 
constitution  of  the  germinal  matter  (or  idioplasm),  inasmuch  as 
this  possesses  an  inherent  tendency  to  perfect  itself  and  to  progress, 
developing  by  a  slow  and  continuous  evolution  new  and  more 
complex  forms,  which  are  independent  to  a  certain  degree  either 
of  •  the  variations  of  the  environment  or  of  the  struggle  f9r 
existence. 

It  is  undeniable  that  all  the  branches  of  the  zoological  trunk 
exhibit  a  progression  from  the  lower  forms  to  the  higher,  and 
always  in  a  sufficiently  cognate  form,  although  the  animals  may 
be  subjected  to  very  different  external  conditions  of  existence  and 
development.  We  see,  for  instance,  that  the  eye,  which  in.  the 
rudimentary  species  of  animals  is  represented  by  a  simple  spot  of 
pigment,  is  provided  in  worms,  in  arthropods,  in  molluscs,  in 
vertebrates,  with  accessory  apparatus,  such  as  the  lens,  the  vitreous 
body,  iris,  choroid,  etc.  This  tendency  towards  perfection,  whether 
of  single  organs  and  apparatus,  or  of  the  individual  as  a  whole, 
which  is  revealed  everywhere  in  the  organic  world,  must,  according 
to  Niigeli  (since  it  is  comparatively  independent  of  extrinsic  vital 
conditions),  find  its  explanation  in  the  very  being  of  the  living 
substance. 

Unlike  Darwinism  and  Lamarckism,  which  accord  a  pre- 
dominating importance  to  external  causes  in  phylogenic  evolution, 
Nagelism  assigns  the  maximal  importance  to  internal  causes. 
Nageli's  phylogenesis  harmonises  perfectly  with  his  ontogenesis. 
The  internal  causes  of  the  transformation  are  perfectly  analogous 
to  those  by  which  the  germ,  or  fertilised  ovum,  develops  into  the 
perfect  individual,  and  the  mutilated  individual  is  capable  of 
regenerating  a  missing  member  (e.g.  a  pollarded  tree  can  recover 
all  its  branches,  a  lizard  can  reproduce  its  lost  tail,  a  decapitated 
snail  can  reproduce  its  head).  It  is  certainly  within  the  intimate 
physico-chemical  structure  of  the  idioplasm  of  the  egg,  or 
mutilated  individual,  and  not  in  the  environment,  that  we  must 
seek  the  determining  cause  of  the  individual  development  or 
reintegration.  So  likewise  the  determining  causes  of  the 
mutability  of  species,  and  of  the  slow  formation  of  new  and  ever 
more  perfect  species,  must  lie  not  in  the  environment,  but  in  the 
intimate  structure  of  the  idioplasm. 

As  in  ontogenic  evolution  the  environment,  in  addition  to 
nutritive  matters,  provides  a  sum  of  stimuli  favourable  to  the 
development  of  hereditary  tendencies ;  so  in  phylogenic  evolution 
the  environment  provides  impulses  favourable  to  the  development 
of  creative  tendencies,  and  in  measure  as  these  develop,  moulds  and 
modifies  them,  adapting  them  to  the  circumstances. 

It  is  not  our  task  to  follow  Nageli  in  the  development  of  his 
theory.  From  the  standpoint  of  general  physiology,  it  suffices  to 
show  that  it  harmonises  perfectly  with  the  principle  we  have 


ii  LIVING  MATTEE  51 

formulated  in  regard  to  the  elementary  vital  activities,  which  are 
all  centred  in  metabolism.  Both  the  reproductive  capacity,  by 
which  the  hereditary  tendencies  are  rapidly  completed,  and  the 
evolutionary  capacity,  by  which  the  creative  tendencies  slowly 
develop,  are  founded  upon  the  metabolic  processes  of  living 
protoplasm. 

The  same  difference  that  we  have  seen  to  exist  between 
automatic  activity  as  depending  essentially  on  internal  impulses 
and  tendencies,  and  reflex  activity  as  due  to  external  stimuli, 
exists  between  Nagelism  and  neo-Lamarckism. 

Starting  from  the  psycho-physical  theorem  that  conscious 
psychical  phenomena  are  the  introspective  aspect  of  correlative 
physiological  excitations,  it  is  not  too  bold  to  assume  that 
unconscious  physiological  phenomena  likewise  have  a  psychical 
aspect  which  is  not  clearly  revealed  to  introspection,  although  it 
helps  to  build  up  the  content  of  consciousness.  With  this  premise, 
it  seems  reasonable  to  admit  with  Hering  that  ontogenic  pheno- 
mena are  the  correlatives  of  an  unconscious  memory  inherent  in 
the  protoplasm ;  just  as  phylogenic  phenomena  might  be  considered 
the  correlatives  of  an  unconscious  formative  imagination. 

Weisinann  (in  1892)  attempted  a  sort  of  reconciliation  between 
Darwinism,  Lamarckism,  and  Nagelism  by  assuming  that  the 
action  of  external  causes  might  be  fixed  in  the  species,  and  become 
hereditary,  if  the  said  action  were  exercised  on  the  plasma  of  the 
germinal  cells.  The  modifications  suffered  by  these  would  manifest 
themselves  in  the  embryo  and  the  adult  individual,  and  would  be 
transmitted  to  the  descendants.  In  this  way  what  Weisinann 
calls  germinal  selection  would  become  possible,  in  which  the  action 
of  external  agents,  combined  with  natural  selection,  would  deter- 
mine the  origin  of  new  species. 

These,  however,  are  merely  ingenious  abstract  speculations, 
which  more  or  less  successfully  disguise  our  impotence  to  determine 
in  any  precise  and  accurate  manner  the  relation  between  the  action 
of  external  causes  and  the  reaction  of  internal  causes,  manifested 
in  the  development  of  a  morphological  process. 

De  Vries  (1901)  thought  to  escape  from  the  many  and 
insuperable  difficulties  of  the  hypotheses  we  have  been  examining 
by  his  Theory  of  Mutations,  according  to  which  new  species 
originate  not  in  a  continuous  variation,  but  in  discontinuous 
variations,  by  sudden  leaps  which  he  termed  mutations.  In 
certain  moments  of  the  life  of  the  species,  under  special  conditions, 
some  individuals  may  unexpectedly  assume  a  series  of  new 
characters,  differing  from  those  possessed  by  their  progenitors,  and 
these  characters  might  be  hereditary. 

Many  well-known  facts  in  the  history  of  plants  and  domestic 
animals  seem  to  prove  the  sudden  origin  of  new  forms,  as  supposed 


52  PHYSIOLOGY  CHAP. 

by  the  theory  of  De  Vries.  The  majority  of  the  new  varieties 
cultivated  in  the  fields,  orchards,  and  gardens,  when  not  obtained 
by  hybridising,  appear  to  have  originated  in  such  unexpected 
mutations. 

These  facts  were  illustrated  and  described,  even  before  De  Vries, 
by  Korschinski,  who  gave  the  phenomena  the  name  of  heter agenesis. 

De  Vries  in  his  famous  experiments  at  the  Botanical  Garden  of 
Amsterdam  saw  several  distinct  species  originate  in  a  few  years 
from  Oenothera  Lamarckiana  —  Oenothera  gigas,  0.  albida,  0. 
rubrinervis,  0.  nanella,  etc.,  species  which  are  said  to  give  rise 
on  direct  fertilisation  to  products  of  a  constant  character.  This 
would  be  the  first  experimental  instance  on  record  of  neo-genesis 
in  species  belonging  to  the  higher  organisms.  Not  all  biologists, 
however,  are  inclined  to  accept  the  conclusion  of  De  Vries.  Many 
(among  them  Bateson,  and  Cuboni  in  Italy)  maintain  that  the 
so-called  new  species  have  no  constant  characters  of  descent,  and 
that  the  new  forms  observed  by  the  illustrious  botanist  of 
Amsterdam  represent  merely  special  cases  of  polyhybridism,  in 
which  the  dominant  and  recessive  elements  of  the  progenital 
forms  separate  out  according  to  Mendel's  Law.  In  favour  of  this 
supposition  we  have  the  fact  that  some  of  the  pollen  grains  of 
Oenothera  Lamarckiana  are  deformed  and  sterile,  as  always  occurs 
with  hybrids. 

If  we  admit  that  the  mutations  observed  by  De  Vries  are  no 
more  than  a  return  to  the  parent  species,  the  fundamental  basis 
of  his  theory  loses  all  evidential  value.  Further,  it  is  undeniable 
that  many  facts  of  systematic  botany,  and  above  all  of  palaeontol- 
ogy, can  be  more  readily  interpreted  on  the  generally  accepted 
theory  of  continuous  variations.  And  lastly,  it  should  be  noted 
that  De  Vries  himself  recognises  that  the  all-essential  point,  i.e. 
the  internal  causes  of  mutation,  still  remains  an  impenetrable 
mystery  to  human  investigation. 

Whatever  the  future  of  the  different  theories  relating  to  the 
mechanism  by  which  the  various  living  forms  have  developed  one 
from  another,  whatever  the  nature  of  the  internal  causes  deter- 
mining the  formation  of  new  species,  it  must  never  be  forgotten 
that  the  Law  of  Descent,  i.e.  the  general  Theory  of  Evolution,  which 
by  means  of  Darwinism  dominated  the  minds  of  scientific  men 
for  half  a  century,  has  been  marvellously  fecund,  and  has  incited  a 
vast  series  of  researches,  leading  to  the  acquisition  of  new  truths, 
which  without  that  theory  might  never  have  been  gathered  up. 
It  therefore  remains  the  corner-stone  of  biological  research ;  even 
more  than  as  a  hypothesis  we  are  constrained  to  admit  it  as  a 
necessary  postulate,  because  its  negation  would  logically  include 
the  negation  of  a  unitary  biological  science. 

.      From  the  foregoing  observations  on  the  vital  activities  common 


ii  LIVING  MATTEE  53 

to  all  living  beings,  we  may  formulate  the  following  general 
propositions  : — 

(a)  All  vital  activity  is  founded  on  the  metabolism  of  living 
matter. 

(&)  As  a  material  exchange,  metabolism  expresses  itself  in 
anabolic  and  katabolic  processes. 

(c)  As  a  dynamic  exchange,  metabolism  manifests  itself  by  the 
accumulation  and  discharge  of  energy. 

(d)  The  anabolic  and  katabolic  processes  express  themselves 
in   the  phenomena  of  nutrition    (consumption  and   repair)   and 
reproduction  (formation  and  evolution  of  germs). 

(e)  The  accumulation  and  transformation  of  energy  is  exhibited 
in  the  phenomena  of  rest  and  excitation  (automatic  or  reflex  in 
character). 

(/)  All  the  processes  of  vital  metabolism  conform  to  the 
conservative  laws  of  heredity,  and  to  the  evolutionary  laws  of 
variability. 

(g)  Vital  metabolism  is  exhibited  under  a  double  aspect : 
to  external  observation  it  manifests  itself  in  somatic  phenomena  ; 
to  introspection  it  reveals  itself  in  psychical  phenomena,  conscious 
and  unconscious. 

V.  On  penetrating  deeper  into  the  study  of  common  vital 
activities,  we  must  inquire  whether,  from  the  standpoint  of  general 
physiology,  it  is  possible  to  differentiate  sharply  between  the  two 
great  kingdoms  of  living  nature — plants,  and  animals. 

In  comparing  what  are  relatively  the  highest  representatives 
of  the  two  kingdoms,  nothing  seems  more,  simple  and  natural  than 
the  distinction  between  a  plant  and  an  animal.  Many  erroneous 
opinions  have,  nevertheless,  been  promulgated  in  the  attempt  to 
define  their  differential  characters.  Of  these  the  principal  are  as 
follows : — 

According  to  Linnaeus,  the  lack  of  sensibility  and  capacity 
for  active  movement  in  plants  is  sufficient  to  distinguish  them 
from  animals.  But  the  case  of  Mimosa  puclica  (Fig.  9),  Dioneci 
muscipula  (Fig.  10),  and  other  sensitive  plants,  whose  leaves 
move  at  the  slightest  contact  with  an  insect,  show  that  excitation 
in  the  form  of  active  movement,  the  external  sign  of  sensibility, 
is  demonstrable  in  plants  also.  Claude  Bernard  (1878)  showed 
that  anaesthetics  (ether  and  chloroform)  act  in  the  same  way  on 
animals  and  on  sensitive  plants. 

Cuvier  was  of  opinion  that  the  existence  in  animals  of  a 
distinct  digestive  apparatus  with  the  accompanying  digestive 
function,  of  which  no  trace  exists  in  plants,  was  a  sufficient  sign 
of  distinction  between  the  former  and  the  latter.  To-day,  however, 
we  know  that  an  immense  number  of  the  lower  animals  have  no 
digestive  tube,  while  on  the  other  hand  the  so-called  insectivorous 
plants,  described  by  Darwin,  possess  organs  capable  of  subjecting 


54 


PHYSIOLOGY 


CHAP. 


animal  substances  to  a  real  digestion.     Papain,  an  enzyme  which 
has  the  same  properties  as  pepsin,  has  been  extracted  from  Carica 


w" 

!•'!<;.  0. — Mlinom  pinlicn.  During  the  day  the  leaves  are  extended,  as^in  A  ;  when  stimulated 
by  .shaking  or  touching,  they  close  up,  drooping  backwards,  as  la  /.'.  After  chloroform 
narcosis  this  reaction  does  not  take  place. 

papaja.  The  juices  of  the  leaves  of  Nepenthes,  Drosera,  and  Dionea 
(Figs.  11  and  12)  digest  meat  to  the  great  advantage  of  the  plant. 
We  know  further  that  plants,  like  animals,  accumulate  sugar, 

starch,  oil,  and  proteins 
as  reserve  nutritive  ma- 
terials, and,  for  nutritive 
purposes  and  to  bring 
them  into  circulation, 
submit  them  to  a  regular 
digestion  by  the  action 
of  certain  enzymes,  such 
as  diastase,  invertin, 
emulsin,  and  the  peptic 
or  hydrolytic  ferments. 

After  Lavoisier  (1777) 
had  demonstrated  that 
animals  absorb  oxygen 
and  exhale  carbonic  acidr 
and  the  Dutch  Ingen- 
housz,  and  almost  contemporaneously  the  Genevans  Senebier  and 
Th.  de  Saussure  (1800),  had  discovered  that  green  plants  reduce 
the  carbonic  acid  of  the  air  by  assimilating  carbon  and  emitting 
oxygen,  a  theory  was  involved  which  predicated  a  functional 
antagonism  between  plants  and  animals.  By  storing  up  the 


Fiu.  10.  -  -  Leaf  of  Dimiett  nm*ripul«.  (Darwin.)  The 
upper  surface  of  the  leaf  shows  the  bristles  that  react 
on  the  slightest  contact  with  an  insect,  provoking  im- 
mediate closure  of  the  two  halves  of  the  leaf,  ami 
capture  of  the  insect,  which  is  then  digested  by  the 
secretion  from  the  glands  upon  the  surface  of  the  leaf. 


II 


LIVING  MATTER 


55 


energy  of  the  sun's  rays,  as  observed  by  J.  R  Mayer  (1845),  plants 

reduce  carbonic  acid  and  form  organic  sub- 

stances,  which  serve  as  fuel  for  the  animals   ^ 

that  constantly  devour  the  plants  and  disperse 

the  energy  stored  up  in  them.     The  plant  is 

accordingly  an  apparatus  for  reduction,  the 

animal  an  apparatus  for  oxidation. 

This  theory  was  more  particularly  devel- 
oped in  France  by  Dumas  and  Boussingault, 

in   Germany  by   Liebig.     There  is  between 

plants  and  animals  a  constant  circulation  of 

matter  and  exchange  of  energy.    The  animal, 

by  means  of  the  oxygen  of  the  air,  transforms 

into  heat,  electricity,  or  motion  the  potential 

energy  contained  in  the  food-stuffs  obtained 

directly  (herbivores)  or  indirectly  (carnivores) 

from  plants,  and  produces  water,  carbonic  acid, 

ammonia  and  salts.     The  plant  draws  these 

ultimate  products  from  the  air  and  soil,  and 

by  means  of  solar  radiation  builds  them  up 

into  carbohydrates,  fats,  and  proteins.   Animal 

life  as  a 
whole  is 
thus  sub- 
ordinated 
to  the  pre- 
existence 
and  co-ex- 
istence of 

plant  life,  the  latter  being  wholly 
independent  of  the  former. 

This  doctrine  of  vital  an- 
tagonism between  plants  and 
animals  is  no  less  false  than  the 
teaching  of  Linnaeus  and  Cuvier, 
as  was  readily  demonstrated  by 
Pfliiger  in  1875.  It  is  a  fallacy 
to  assume  any  radical  difference 
of  function  between  plant  and 
animal  protoplasm.  In  the  last 
chapter  we  saw  that  both  kinds 

Fi«.12.-.Leaf  of  Drosera  rotundifolm     (Darwin  )  Qf   protoplasm  differentiate  into 
The     leaf     shows     numerous     pedunculated  Jr 

glands,  each  having  at  its  extremity  a  drop  Cells     01'     elementary    Organisms 
of  secretion  which  serves  to  catch  and  digest          j  j          -,-1  ,-    ii 

the  insect.  endowed   with    an    essentially 

analogous  structure  and  com- 
position. In  considering  the  vital  characters  common  to  all 
living  beings  we  recognised  both  in  plant  and  in  animal  metabolism 


Fj(i.  11.  —  Ascidiuni  of  leaf 
of  Nepenthes.  At  the- 
bottom  of  the  pitcher- 
shaped  receptacle  is  seen 
the  fluid  F,  secreted  by  the 
glands,  in  which  the  ani- 
malcules that  fall  in  can 
be  digested.  This  figure 
is  somewhat  reduced. 


56  PHYSIOLOGY  CHAP. 

a  double  process,  anabolic  and  katabolic :  the  first  synthetic,  re- 
ducing, assimilatory ;  the  second  analytic,  oxidising,  disintegrative. 

The  antagonism  apparent  at  the  extreme  limits  of  function 
between  -the  higher  plants  and  animals  becomes  less  and  less  in 
proportion  as  we  descend  the  scale  of  the  two  groups  of  living 
beings.  On  comparing  the  simplest  animal  and  plant  organisms, 
it  is  impossible  to  trace  a  sharp  line  of  demarcation  between  the 
two  kingdoms.  This  fact  demonstrates  their  common  origin, 
according  to  the  Unitary  Theory  of  Life,  by  which  plants  and 
animals  must  be  regarded  as  two  divergent  stems  arising  from 
a  common  trunk  represented  by  the  simplest,  or  primitive,  living 
forms,  to  which  Haeckel  gave  the  name  of  Protista. 

The  fallacy  of  this  supposed  antagonism  between  the  functions 
of  plants  and  animals  lies  in  a  confusion  between  the  katabolic,  re- 
spiratory function,  chemically  represented  by  processes  of  oxidation, 
which  is  common  to  all  living  beings,  and  the  anabolic,  chloro- 
phyllic  function  which  is  peculiar  to  the  green  parts  of  plants. 
Vegetable  protoplasm,  including  that  provided  with  chlorophyll, 
breathes  like  animal  protoplasm,  i.e.  it  absorbs  oxygen  and  gives 
off  carbonic  acid,  when  removed  from  the  action  of  the  sun's  rays. 
Under  the  influence  of  these  rays,  it  breathes  in  the  reverse  sense, 
i.e.  it  absorbs  carbonic  acid  and  gives  off  oxygen",  because  the 
reducing  function  of  the  chlorophyll,  which  is  actively  aroused  by 
the  soLir  radiation,  exceeds  in  its  activity  the  respiration  proper, 
and  masks  its  effects. 

It  has  long  been  known  that  the  presence  of  oxygen  is  almost 
always  essential  to  plant  as  to  animal  life.  As  early  as  1822,  De 
Saussure  was  aware  that  the  most  vigorous  plants,  such  as  the 
Cactus,  die  quickly  when  brought  into  an  atmosphere  deprived  of 
oxygen.  P.  Bert  found  that  wheat  germinated  less  freely  in 
proportion  as  the  oxygen  tension  of  the  air  in  which  it  was  kept 
was  lowered. 

So,  too,  when  tension  of  carbon  dioxide  reaches  an  excessive 
degree  it  is  as  harmful  to  plant  as  to  animal  life.  It  was,  again, 
De  Saussure  who  demonstrated  that  plants  brought  into  an 
atmosphere  of  C02  perished.  An  atmosphere  containing  \  of 
carbonic  acid  is  sufficient  to  check  the  germination  of  most  plants  ; 
accordingly,  respiration  as  an  oxidative  process  is  a  function  as 
indispensable  to  the  life  of  plants  as  to  animals. 

The  antagonism  that  is  sometimes  proposed  between  plants 
and  animals  is  therefore  fallacious,  and  derives  from  the  fact  that 
the  former  accumulate  the  energy  elaborated  from  the  sun's  rays, 
while  the  latter  consume  it,  or  transform  it  into  special  forms  of 
heat  and  motion. 

It  is  in  general  true  that  plants  cool  the  surrounding  atmo- 
sphere, while  animals  raise  the  temperature ;  but  this  is  due  to  the 
fact  that  respiration  is  not  usually  very  intense  in  plants,  and 


ii  LIVING  MATTEE  57 

is  associated  with  a  considerable  transpiration  of  water,  by  which 
a  large  amount  of  heat  is  rendered  latent,  so  that  the  plants 
as  a  rule  become  cooler  than  their  environment.  But  when  tran- 
spiration is  checked,  or  when  plants  which  are  breathing  actively 
are  observed,  they  are  found  to  develop  as  much  heat  as  animals. 
For  instance,  on  bringing  together  a  mass  of  germinating  peas,  a 
rise  of  temperature  of  some  2°  C.  above  the  surrounding  atmosphere 
can  be  detected  ;  a  rise  of  15°  C.  was  measured  in  the  large  flowers 
of  the  Victoria  Regia. 

Lastly,  it  should  be  noted  that  if  all  animals  live  directly,  or 
indirectly,  on  the  elements  provided  by  the  vegetable  kingdom,  it 
is  not,  on  the  other  hand,  true  that  all  plants  live  on  the  inorganic 
substances  provided  exclusively  by  the  soil,  air,  and  water.  A 
great  number  of  plants,  lacking  in  chlorophyll,  live  saprophy  tically 
at  the  expense  of  the  organic  substances  of  plant  residues  and  dead 
animals,  or  parasitically  at  the  cost  of  other  living  things.  Such 
are  the  Schizomycetes  and  Fungi,  properly  so-called.  As  the  life 
of  animals  is  subordinated  to  that  of  plants,  so  the  life  of  this 
innumerable  vegetable  host  is  subordinated  to  that  of  animals  or 
other  plants. 

VI.  Since  antagonism  between  the  vital  activities  of  plants 
and  animals  is  excluded,  it  follows  logically  that  the  functional 
differences  which  exist  between  the  two  great  kingdoms  of  living 
Nature,  and  which  are  very  apparent  in  the  higher  classes,  must 
consist  in  the  different  manifestations  in  the  two  kingdoms  of 
Metabolism,  which  underlies  all  vital  phenomena.  It  is  evident 
that  the  anabolic  processes  are  predominantly  developed  in  plants, 
the  katabolic  processes  in  animals. 

The  fact  above  emphasised,  that  all  animals  require  for  their 
nutrition  organic  matters  (proteins,  fats,  and  carbohydrates) 
already  formed  by  other  animals  or  plants,  shows  that  their 
anabolic  capacities  do  not  extend  to  synthesis  of  these  substances 
from  inorganic  materials.  The  majority  of  plants,  on  the  contrary, 
can  live  and  flourish  on  exclusively  inorganic  matter,  showing 
that  their  anabolic  capacity  is  strong  enough  to  enable  them  to 
make  this  synthesis. 

The  anabolic  capacity  seems  to  be  most  highly  developed  in 
the  group  of  the  so-called  nitrifying  bacteria,  which  in  recent 
years  have  aroused  great  interest  among  physiologists.  Devoid  of 
chlorophyll,  they  are  none  the  less  able,  independent  of  the  action 
of  the  sun's  rays,  to  form  by  synthesis  all  the  organic  substances 
which  they  require  for  their  development  and  reproduction,  given 
the  inorganic  materials  provided  by  the  soil  and  the  air.  More 
wonderful  still,  some  of  them,  on  closer  observation,  are  found  to 
be  capable  of  synthetically  forming  organic  nitrogenous  matter  by 
absorption  of  free  nitrogen  from  the  air  and  soil.  Among  these  is 
Clostridium  pasteurianum,  studied  by  Winogradsky,  which  utilises 


58 


PHYSIOLOGY 


CHAP. 


carbonic  acid  or  the  carbonates  of  the  soil  to  form  carbohydrates, 
and  free  nitrogen  to  form  proteins.  No  less  interesting  are  the 
various  forms  of  Rhizobium  leguminosarum,  studied  by  Hellziegel, 
Nobbe,  Beyerinck,  Franck  and  others,  which  penetrate  the  root- 
hairs  of  the  common  Leguminosae  (beans,  peas,  lupins,  trefoils,  etc.), 
and  produce  hypertrophy  in  the  form  of  nodules  or  tubercles 

containing  a  fungoid  mass,  consisting 
of  bacteria  for  the  most  part  of  excep- 
tional size,  with  a  less  number  of  normal 
form  and  proportions  (Fig.  13).  Accord- 
ing to  the  said  authors,  the  rhizobium 
lives  in  symbiosis  with  the  leguminous 
plant.  The  latter  provides  the  bacterium 
with  carbohydrate  ;  and  the  bacterium, 
by  conversion  of  the  free  nitrogen  into 
an  organic  form,  provides  the  leguminous 
plant  with  the  nitrogenous  compounds 
required  for  the  synthetic  formation  of 
proteins,  thus  promoting  the  general 
welfare  of  the  plant. 

In  the  greater  number  of  cases, 
however,  the  assimilation  of  carbon  is  an 
anabolic  function  of  green  plants,  which 
are  capable  of  reducing  the  carbonic  acid 
of  the  air  by  means  of  chlorophyll,  under 
the  influence  of  the  luminous  rays  of 
the  sun  (particularly  of  the  less  refran- 
gible red  and  yellow  rays)  ;  and  the 
assimilation  of  nitrogen  is,  generally 
speaking,  due  in  plants  to  reduction  of 
the  nitrates  contained  in  the  humus, 
and  not  to  intake  of  free  nitrogen.  The 
clearest  demonstration  of  this  fact  is 
aforded  by  .  the,  ™lti™tion  of  green 

plants  in  artificial  SOUltlOnS  which,  With 

the  exception  of  carbon,  contain  all  the 
chemical  elements  that  participate  in  the  formation  of  living 
matter,  in  the  form  of  combinations  of  salts.  The  formula  given 
by  Sachs  for  this  artificial  nutrient  fluid  is  as  follows  :  — 


Fl 


ously  provide.!  with  nodules—  the 


Water  . 

Potassium  nitrate 
Sodium  chloride  . 
Potassium  sulphate 
Magnesium  sulphate 
Calcium  phosphate 
Ferrous  sulphate  . 


1000-0 
1-5 
0-5 
0-5 
0-5 
0-5 
0-005 


If  a  grain  of  maize  is  placed  in  this  solution  to  germinate,  the 


II 


LIVING  MATTEE 


59 


experiment  being  carried  out  in  a  glass  jar  (as  shown  in  Fig.  14), 

the  plant,  under  the  influence  of  light,  will  develop  normally, 

flower,  and  bear  fruit.    If  the  iron  sulphate 

is  wanting  in  the  solution,  the  plant  may 

live  for  some  time,  but  its  leaves  will  be 

colourless,  and  under  the  microscope  show- 
absence  of  chlorophyll;  if  the  other  salts 

are  wanting,  the  plant  will  not  germinate, 

or  perishes  as  soon  as  it  develops. 

This  experiment   proves   that   all  the 

carbon  assimilated  by  the  plant  is  derived 

from  the    carbonic  acid   of  the   air — the 

grand  discovery  of  Ingenhousz  ;  further,  it 

shows  that   the  assimilation  of  carbon  is 

conditioned  by  chlorophyll,  the  molecules 

of  which  contain  iron  ;  lastly,  the  assimila- 
tion of   nitrogen  is  due  to  the  reduction 

of  nitrates,  and  the  assimilation  of  sulphur 

and  phosphorus  to  the  reduction  of  sulphates 

and  phosphates. 

The  intimate  processes  by  which  the 

plant  succeeds,  by  the  assimilation  of  all 

these    elements,  in    synthetically  forming 

organic  substances  are  for  the  most  part 
unknown.  Thanks, 
however,  to  the  work  of 
Sachs,  we  know  some- 
thing of  the  process  of 
starch  formation  in  the 

green  parts,  which  may  be  taken  as  the  starting- 
point  for  all  other  synthetic  processes  in  plants. 
In  the  adult  cell,  chlorophyll  is  contained  within 
special  ellipsoidal  corpuscles  known  as  chloro- 
plasts,  which  are  for  the  most  part  found  in 
ift-3— «  great  numbers  heaped  against  the  parietal  proto- 
W~T  plasm  (Fig.  15).  After  a  green  plant  has  been 
exposed  for  a  few  minutes  to  full  sunlight, 
starch  granules  are  seen  to  appear  in  the  middle 
or  edge  of  the  chloroplasts,  which  gradually 
increase  in  size  until  their  volume  exceeds  that 
of  the  chloroplasts.  During  the  night,  when 
starch  formation  is  suspended,  this  accumula- 
tion is  dissolved  by  the  action  of  diastatic  fer- 
ments, and  conveyed  under  the  form  of  sugar 

to  the  parts  in  which  it  can  be  utilised  as  food  material. 

Starch  represents  the  principal  nutritive  reserve  material  that 

accumulates  in  a  solid  form  in  the  plant  cells  in  which  it  is  formed. 


;.  14.  —  Zra  mais  in  culture 
solution.  Mg.,  grain  of  maize ; 
.S'7!.,  Sachs'  nutrient  solu- 
tion ;  *,  cork  to  support  plant 
in  vertical  position. 


FIG.  15.— Two  leaf-cells  of 
Funaria  hygrometrica. 
cl,  chloroblasts  ;  n, 
nucleus.  Magnification, 
300  diameters. 


£0  PHYSIOLOGY  CHAP. 

Many  monocotyledons  normally  exhibit  no  formation  of  starch, 
but  produce  sugar  in  solution  ;  it  is  only  when  this  is  in  excess 
that  starch  in  the  solid  form  is  manufactured. 

The  other  organic  matters,  fats  and  proteins,  are  formed  by 
gradual  chemical  change  from  the  carbohydrates,  starch  and  sugar. 
The  formation  of  oil  from  starch  may  be  directly  observed  in  the 
seeds  of  certain  plants.  Paeony  seeds,  for  instance,  so  long  as 
they  are  immature,  contain  only  carbohydrates  and  scarcely  any 
fat.  When  placed  in  moist  air,  it  is  found  after  a  time  that  all 
the  starch  has  disappeared  by  conversion  into  oil.  In  many  of 
the  lower  plants,  e.g.  Algae,  the  first  visible  product  in  the  cell  is 
not  starch  but  oil. 

Far  more  complex  is  the  synthesis  of  proteins  and  nucleo- 
proteins  effected  by  the  roots  from  the  carbohydrates  and  derivatives 
of  the  nitrates,  sulphates,  and  phosphates 
of  the  soil.  We  know  nothing  about  this 
marvellous  synthesis,  indispensable  as  it 
is  to  the  nutrition  and  development  of 
living  protoplasm.  It  is  only  known  that 
oxalic  acid  (C2H204)  is  frequently  formed 
as  a  secondary  product,  which,  in  itself 
toxic,  combines,  as  it  is  formed,  with  lime 

FIG.  K;.  —  ceiis  of  Beer  Yeast  into  an  insoluble  innocuous  salt  that 
collects  in  the  form  of  a  crystalline 
powder  round  those  parts  of  the  plant  in 
which  the  formation  of  proteins  and  nucleins  takes  place.  It 
also  seems  probable  that  asparagine  (C4H8N203),  a  soluble  and 
diffusible  ammo-body,  is  an  intermediate  product  in  protein 
synthesis. 

From  the  green  plants  one  must,  in  virtue  of  their  metabolism, 
distinguish  all  those  plants  which  are  lacking  in  chlorophyll,  and 
live  as  saprophytes,  or  parasites,  or  again  as  parasites  and  sapro- 
phytes according  to  circumstances.  The  innumerable  host  of 
fungi  and  bacteria  come  under  this  category.  They  have  the 
singular  property  of  consuming  in  their  nutrition  and  reproduction 
only  the  minimal  part  of  the  organic  matters  which  form  their 
food,  and  of  destroying  all  the  rest  by  processes  of  fermentation 
and  putrefaction,  effected  by  enzymes  contained  within  the  cell  or 
secreted  from  without. 

A  classical  example  of  this  mode  of  metabolism  is  afforded 
by  Saccharomyces  cerevisiae  (Fig.  16),  which  produces  alcoholic 
fermentation  of  glucose  according  to  the  equation  : 


When  a  certain  quantity  of  yeast  is  introduced  into  grape 
juice,  there  is  formed  along  with  the  development  of  carbonic  acid 
and  the  production  of  alcohol  a  small  amount  of  glycerin,  of 


n  LIVING  MATTEK  61 

succinic  acid,  and  of  various  ethers,  which  eventually  inhibit 
fermentation  and  bring  it  to  a  standstill.  The  quantity  of  yeast 
which  is  then  deposited  at  the  bottom  of  the  vessel  is  conspicuously 
augmented,  showing  that  the  cells  of  the  Saccharomyces  have 
abundantly  reproduced  themselves;  but  the  organic  nutritive 
matters  contained  in  the  grape  juice  would,  if  they  had  not  been 
decomposed  by  the  fermentative  process,  have  sufficed  for  the 
nutrition  and  multiplication  of  an  incomparably  larger  amount  of 
yeast. 

Many  pathogenic  or  non-pathogenic  bacteria  are  able  to  dis- 
solve gelatin  or  coagulated  albumin  for  their  nutrition  and  multi- 
plication, and  effect  a  putrid  decomposition  of  the  various  culture 
fluids  or  media,  with  development  of  carbonic  acid,  sulphuretted 
hydrogen,  ammonium  sulphate,  ammonia,  and  a  simultaneous  forma- 
tion of  new  substances  which  generally  have  a  toxic  action,  and  are 
the  cause  of  virulent  disease. 

In  general  those  plants  that  contain  no  chlorophyll,  and  require 
for  their  nutriment  the  organic  matters  already  formed  by  other 
plants  or  animals,  utilise  these  substances  merely  as  the  raw 
material  of  nutrition,  submitting  them  further  to  special  chemical 
transformations.  Fungi  and  bacteria,  indeed,  can  adapt  previously 
inadequate  substances  to  their  nutrition.  By  means  of  invertase 
they  transform  saccharose  into  glucose,  by  diastase  starch  is  turned 
into  sugar,  with  the  trypsin  and  pepsin  ferments  albumin  is  con- 
verted into  albumoses  and  peptone.  Fungi  have  been  proved  to 
nourish  in  very  different  culture  media,  and  are  capable,  with  the 
help  of  the  organic  compounds  of  carbon,  and  nitrogenous  mineral 
salts,  of  building  up  synthetically  all  the  highly  complex  products 
essential  to  the  formation  of  protoplasm.  They  represent,  accord- 
ingly, in  their  metabolism  an  intermediate  group  .between  the 
chlorophyll-containing  plants  and  animals. 

The  anabolic  capacity  of  all  animals,  without  exception,  is 
limited  to  the  elaboration  of  the  three  principal  groups  of  organic 
substances,  and  their  conversion  into  living  protoplasm,  with  the 
further  synthetic  formation  of  new  substances  which  do  not  exist 
in  the  plant  world.  They  are  incapable  of  reducing  fully  oxidised 
organic  substances  so  as  to  produce  carbohydrates,  fats,  and 
proteins;  but  they  have  the  power  (as  we  shall  be  able  to 
demonstrate  fully)  of  transforming  carbohydrates  into  fats,  albu- 
inoses  and  peptones  into  true  proteins. 

Within  the  animal  kingdom  again  we  can  distinguish  different 
groups,  according  to  their  nutritive  requirements  and  correspond- 
ing metabolism.  Herbivores  and  frugivores  more  particularly 
need  to  supplement  the  proteins  with  the  carbohydrates  in  which 
vegetable  food  is  superabundant ;  insectivores  and  carnivores,  on  the 
contrary,  profit  by  the  many  fats  which  abound  in  animal  food. 
Neither  fats  nor  carbohydrates,  however,  are  absolutely  indis- 


62  PHYSIOLOGY  CHAP. 

pensable  to  life.  Some  animals  have  adapted  themselves  to  a 
purely  protein  diet,  and,  further,  to  a  single  form  of  the  same. 
Thus,  e.g.,  the  clothes-moth  lives  exclusively  on  the  keratin  of 
which  the  hairs  of  the  wool  or  fur  consist,  and  from  which  it 
derives  all  that  is  necessary  for  the  construction  of  its  protoplasm. 
Again,  as  we  shall  see,  it  is  possible  to  keep  a  dog  alive,  and  in  its 
normal  state,  on  a  purely  flesh  diet,  while  this  is  found  impossible 
on  an  exclusive  diet  of  fats  and  carbohydrates,  no  matter  how 
abundant. 

The  chief  part  of  the  mineral  substances  which  enter  into  the 
chemical  composition  of  animals  cannot  be  assimilated  as  such,  but 
only  when  they  are  present  in  organic  combinations,  as,  e.g.,  the 
calcium  phosphate  of  milk  casein,  the  potassium  salts  of  muscle 
protein.  If  mice  are  fed  on  casein  from  which  the  greater  part  of 
the  salts  contained  in  the  organic  combinations  of  milk  have  been 
previously  washed  out,  and  if  sugar  be  added,  as  well  as  all  the 
salts  contained  in  the  ashes  of  milk  in  a  non-organic  form,  the 
mice  perish  slowly  during  this  diet,  and  succumb  after  about  forty 
days  (Lunin).  This  and  similar  experiments  on  artificial  feeding 
in  other  animals,  show  that  they  are  only  capable  to  a  small 
extent  of  assimilating  inorganic  substances,  i.e.  of  binding  them 
synthetically  into  the  protein  molecule  on  which  the  living 
protoplasm  is  nourished. 

BIBLIOGRAPHY 

The  following  may  be  consulted  for  the  literature  of  the  Theory  of  Evolution  : — t 
LAMARCK.     Philosophic  zoologique.     Paris,  1809. 
CHARLES  DARWIN.     On  the  Origin   of  Species  by  Means  of  Natural  Selection. 

London,  1859. 

C.  VON  NAGELI.    Mechanisch-physiologische  Theorie  der  Abstammungslehre.   1884. 
WKISMANN.     Das  Keirnplasrne  :  eine  Theorie  d.  Vererbung.     Jena,  1892. 
H.  DE  VRIKS.     Die  Mutationstheorie.     Leipzig,  1901,  1903. 
YVES  DELAGE.    L'Heredite  et  les  grands  problemes  de  la  biologie  generale.     Paris, 

1903. 

DETTO.     Die  Theorie  d.  direkten  Anpassung.     Jena,  1904. 
PAULY.     Darwinisnius  und  Lamarckismus.     Munich,  1905. 
LOTSY.     Vorlesungen  iiber  Deszendenztheoricn.    Jena,  1906. 
SCHNEIDER.     Einfuhrung  in  die  Deszendenztheorie.     Jena,  1906. 
RIGNANO.     Sur  la  transmissibilite  des  caracteres  acquis.     Paris,  1906. 

The  two  following  text-books  may  be  consulted  for  the  general  physiology  pf 
plants,  and  their  characteristics  as  distinct  from  animals  : — 

E.   STRASBURGER,  F.   NOLL,   H.   SCHENCK,  A.  F.   W.   SCHIMPER.     Lehrbuch  d. 

Botanik.     Jena.     G.  Fischer,  5th  ed.,  1902. 

W.  PFEFFER.     Lehrbuch  d.  Pnanzenphysiologie.     Leipzig,  1897-1901. 
Recent  English  Literature  of  the  subject  : — 

W.  PFEFFER.     The  Nature  and  Significance  of  Functional  Metabolism  in  the  Plant. 

Proc.  Roy.  Soc.,  London,  1898,  Ixiii.  93. 
K.  PEARSON.     Data  for  the  Problem  of  Evolution  in  Man.    Proc.  Roy.  Soc. ,  London, 

1900,  Ixvi.  23,  316. 
K.PEARSON.     Mathematical  Contributions  to  the  Theory  of  Evolution.     Proc  Roy 

Soc.,  London,  1900,  Ixvi.  140. 


ii  LIVING  MATTEE  63 

W.  BATESON.     Heredity,  Differentiation,  and  other  Conceptions  of  Biology.    Proe. 

Roy.  Soc.,  1901,  Ixix.  193. 

T.  M.  BALDWIN.     Development  and  Evolution.     London  &  New  York,  1902. 
A.  K.  MARSHALL,  E.  B.  POULTON,  etc.     Five  Years' Observations  and  Experiments 

(1896-1901)  on  the  Bionomics  of  South  Africa  Insects.     Trans.  Entom.  Soc., 

London,  1902,  p.  287. 
K.  PEARSON.     Mathematical  Contributions  to  the  Theory  of  Evolution.     Proc.  Roy. 

Soc.,  London,  1902,  Ixix.  330  ;  1903,  Ixxi.  288. 
A.  R.  WALLACE.     Darwinism  :  Exposition  of  the  Theory  of  Natural  Selection  with 

some  of  its  Applications.     London,  Macmillan.  1902. 
W.   F.  R.  WELDON.     Professor  de  Yries  on  the  Origin  of  Species.     Biometrika, 

1902,  i.  365. 

TH.  M.  MORGAN.     Evolution  and  Adaptation.     New  York,  1903. 
W.    BATESON.     Opening  Address  at  the  British  Association  (Zoology).     Nature, 

•1904,  Ixx.  406,  539. 
A.  D.  DARBISHIRE.     On  the  bearing  of  Mendelian  Principles  of  Heredity  on  Current 

Theories  on  the  Origin  of  Species.     Manchester  Lit.  Phil.  Soc.,  1904,  xlviii. 
A.  S.  PACKARD.     The  Origin  of  the  Markings  of  Organisms  (poecilogenesis)  due  to 

the  Physical  rather  than  to  the  Biological  Environment  ;  with  criticism  of  the 

Bates-Miiller  hypotheses.     Proc.  Amer.  Phil.  Soc.,  1904,  xl.  393. 
R.  C.  PUNNETT.     Merism  and  Sex  in  spinax  niger.     Biometrika,  1904,  iii.     Part 

IV.,  p.  313. 
A.  E.   BROWN.     The  Utility  Principle  in  Relation  to  Specific  Characters.     Proc. 

Ac.  Nat.  Sc.,  Philad.,  1905,  Ivii.  206. 
E.   S.  CONKLIN.     The  Mutation  Theory  from  the  Standpoint  of  Cytology.     Sc., 

N.S.,  1905,  xxi.  525. 
H.  E.   CRAMPTON.     On  a  General  Theory  of  Adaptation  and  Selection.     Journ.  of 

Exper.  Zool.,  1905,  ii.  425. 
C.  B.  DAVENPORT.     Evolution  without  Mutation.     Journ.  of  Exper.  Zool..  1905, 

ii.  137. 
W.  S.  HARWOOD.     New  Creations  in  Plant  Life  :  an  Account  of  the  Life  and  Work 

of  Luther  Burbank.     New  York,  1905. 

N.  DE  VRIES.     Species  and  Varieties.     Chicago,  Open  Court,  1905. 
R.  H.  LOCK.     Recent  Progress  in  the  Study  of  Variation,  Heredity,  and  Evolution. 

London,  1906,  xv.  299  pp. 
C.  U.  MERRIAM.     Is  Mutation  a  Factor  in  the  Evolution  of  the  High  Vertebrates  ? 

Science,  1906,  p.  241. 


CHAPTER  III 

LIVING   MATTER :    CONDITIONS    BY    WHICH    IT    IS    DETERMINED 

CONTENTS. — 1.  Nutrition  the  necessary  external  condition  of  vital  metabolism. 
Phenomena  of  inanition.  2.  Importance  of  water.  Latent  life  and  anabiosis. 
y.  Importance  of  oxygen.  Aerobic  and  anaerobic  life.  4.  External  temperature 
indispensable  to  life.  5.  Total  pressure  of  air  and  water,  and  partial  pressure  of 
oxygen  and  carbonic  acid.  6.  External  stimuli.  7.  Chemical  stimuli.  Cherno- 
taxis.  8.  Mechanical  stimuli.  Barotaxis.  9.  Thermal  stimuli  :  thermotaxis. 
10.  Photic  stimuli.  Phototaxis  and  Heliotaxis.  11.  Electrical  stimuli.  Galvano- 
taxis.  12.  The  various  biological  zones  of  ocean  life  (Plankton).  13.  Internal 
conditions  and  stimuli  of  metabolism.  Theory  of  automatism.  14.  Hypotheses 
to  explain  the  intimate  mechanism  of  living  matter.  Bibliography. 

Two  orders  of  conditions,  external  and  internal,  are  essential  to 
the  maintenance  of  metabolism.  Both  the  one  and  the  other  may 
act  directly  or  indirectly.  The  former  cannot  fail  without  cessation 
of  life,  nor  the  latter  without  modifications  and  disturbances  of 
vital  phenomena.  If  we  were  acquainted  with  all  the  internal  and 
external  conditions  of  life,  the  task  of  Physiology  would  be 
terminated  ;  the  "  conditioned,"  i.e.  Life,  would  be  perfectly  known 
to  us. 

Not  all  the  vital  conditions  are  essential  in  the  same  degree  to 
every  living  being.  Each  organism  has  special  requirements  in 
virtue  of  which  it  lives  and  flourishes.  Each  living  species,  there- 
fore, demands  special  treatment.  From  the  standpoint  of  general 
physiology  we  have  only  to  consider  in  broad  outlines  the  most 
universal  and  best  known  of  the  vital  conditions. 

I.  The  first  and  most  general  external  condition  of  metabolism 
is  Nutrition,  i.e.  the  sum  of  the  chemical  materials  essential  to  the 
building-up  of  living  protoplasm. 

We  saw  in  the  last  chapter  how  various  were  the  chemical 
forms  of  the  foods  necessary  to  different  groups  of  living  beings — 
to  nitrifying  bacteria,  green  plants,  saprophytic  and  parasitic  fungi, 
herbivorous  and  carnivorous  animals.  To  this  we  may  add  that 
in  accordance  with  the  chemical  composition  of  the  nutritive 
medium,  the  various  elementary  organisms  react  very  differently. 
Some  can  only  live  in  fresh  water ;  others  in  salt  water.  All  die 
more  or  less  rapidly  when  brought  into  distilled  water.  Every 

64 


CHAP,  in 


LIVING  MATTER 


65 


simple  or  complex  organism,  indeed,  exhibits  a  certain  capacity  of 
adapting  itself  to  an  environment  and  nutrition  different  from 
those  to  which  it  has  been  accustomed,  provided  only  that  the 
change  is  effected  very  slowly  and  gradually.  In  consequence  of 
this  adaptation,  temporary  modifications  of  the  specific  characters 
ensue.  According,  however,  to  certain  experiments  of  Nageli, 
these  are  not  persistent,  but  quickly  disappear  when  the  organism 
is  brought  back  to  its  original  environment  and  alimentation. 

In  order  to  form  an  adequate  concept  of  the  adaptability  of 
various  organisms  to  unusual  conditions  in  respect  of  nutrition, 
we  .  may  refer  to  certain  bacteria,  recently  investigated  by 
Winogradsky,  which  he  calls  sulphur  or  iron  bacteria.  The 
sulphur  bacteria  are  represented  by  a  family  of  microbes,  which 
can  only  live  in  the  water  of  bogs  or  marshes,  where,  owing  to  the 
decomposition  of  vegetable  and  animal  matters,  there  is  a  great 
development  of  hydrogen  sulphide.  This  they  absorb,  oxidising  it, 
and  setting  free  the  sulphur,  which  they  accumulate  in  the  body 
of  their  cells  in  the  form  of  highly  refractive  granules.  On 
subsequent  oxidation,  these  granules  give  rise  to  a  formation  of 
sulphuric  acid,  which  is  excreted  as  such.  The  iron  bacteria  live 
in  marshy  water,  where  ferrous  carbonate  is  found  in  solution  ; 
this  they  take  up,  and  convert  it  into  ferric  carbonate,  which  readily 
decomposes  on  excretion,  and  the  precipitate  of  iron  oxide  forms 
the  ochre-like  deposit  known  as  meadow-ore. 

Both  sulphur  and  iron  bacteria  perish  when  brought  into 
spring  water,  which  contains  no  hydrogen  sulphide  or  ferrous 
carbonate,  while  these  compounds  act  as  poisons  to  all  other  living 
beings.  They  must,  therefore,  have  undergone  a  permanent  adapta- 
tion to  a  quite  exceptional  form  of  environment  and  nutrition. 

Whatever  the  nature  of  the  food-stuffs  appropriate  to  the 
various  organisms,  they  are  indispensable  to  the  maintenance  of 
life.  Absolute  or  relative  deprivation 
of  food  produces  a  state  of  inanition, 
during  which  the  organism  primarily 
consumes  the  reserve  materials  stored 
up  in  the  body  of  the  cell,  and  then 
absorbs  its  own  protoplasm,  shrinking 
more  and  more,  until  it  finally  perishes 
when  the  protoplasm  has  no  longer 
enough  potential  energy  to  maintain  the 
balance  of  metabolism  (Fig.  17). 

The  individual  living  elements  of 
which  the  tissues  and  organs  of  the 
higher  animals  are  composed  draw  all 
their  nourishment  from  a  common  fluid, 
the  lymph,  which  circulates  in  the  interstices  of  the  tissues. 

During  inanition,  the  total  consumption  of  the  organism  is  not 

VOL.  I  F 


prived  of  granules.  Magnification, 


66  PHYSIOLOGY  CHAP. 

equally  distributed  among  the  different  tissues ;  a  sort  of  struggle 
for  existence  goes  on  between  them,  some  being  consumed  and 
liquefied  for  the  benefit  of  others,  which  continue  to  exist  as 
parasites,  and  are  even  able  to  reproduce  themselves  (Luciani). 
The  process  of  inanition  in  the  higher  animals  and  man  wjll, 
however,  be  treated  in  detail  later  on. 

II.  Another  condition  no  less  indispensable  to  metabolism 
is  water,  which  infiltrates  the  living  protoplasm  in  large  quantities, 
rendering  it  soft  or  semi-fluid.  In  order  to  realise  the  importance 
of  water  to  the  vital  functions,  we  need  only  consider  the 
consequences  of  natural  or  artificial  desiccation  in  unicellular 
organisms.  Within  certain  limits  the  intensity  of  metabolism 
increases  or  decreases  with  the  increase  or  decrease  of  the  water 
content  of  the  living  matter,  while  beyond  those  limits  vital 
activity  ceases  altogether.  In  the  great  majority  of  plants, 
natural  dryness  of  environment  is  sufficient  to  cause  death.  Many 
mosses,  lichens  and  algae,  however,  which  live  on  naked  rocks  are 
able  to  support  the  drought  of  summer  without  injury.  Seeds 
and  spores,  in  particular,  when  removed  from  the  plant,  may  be 
kept  in  a  dry  state  without  losing  their  capacity,  for  germination. 
It  was  formerly  stated  that  the  wheat  found  with  the  Egyptian 
mummies  retained  its  power  of  germinating  after  more  than  two 
thousand  years;  but  this  fact  was  disproved  by  the  famous  Egypto- 
logist Mariette.  It  has,  however,  been  demonstrated  that  spores 
of  mosses  and  the  seeds  of  Mimosae,  kept  in  a  dry  state  for  over 
sixty  years  in  a  herbarium,  were  perfectly  capable  of  germination ; 
other  seeds,  on  the  contrary,  lose  their  vitality  after  one  year, 
others  again  after  a  few  days,  while  others  will  not  tolerate  any 
desiccation,  e.g.  the  seeds  of  Salix. 

Some  groups  of  animals  can  be  kept  for  years  in  a  desiccated 
state  without  losing  the  faculty  of  awakening  to  life  a  few 
moments  after  they  are  moistened  again  (Preyer's  anabiosis). 
Among  these  are  the  so-called  Jftoti/erae,  small  crustaceans,  and  the 
Tardegrada,  arachnoids  resembling  mites,  which  live  in  the  moss 
and  dust  of  roofs,  as  discovered  by  Leeuwenhoek  (1719),  who  first 
described  this  remarkable  phenomenon.  Also  the  Anguillulae 
of  mildewed  wheat,  on  which  Spallanzani  (1776)  made  many 
curious  experiments  of  repeated  anabiosis.  Lastly,  the  greater 
part  of  the  bacteria,  particularly  in  the  spore  state,  come  under 
the  same  category. 

It  is  not  easy  in  any  of  these  cases  of  apparent  death  to 
determine  whether  there  is  absolute  suspension  of  metabolism,  a 
true  latent  or  potential  life,  or  a  metabolism  reduced  to  the 
lowest  terms,  i.e.  to  the  state  which  Spallanzani  was  the  first  to 
characterise  as  minimal  life.  To  decide  the  question,  it  is  neces- 
sary to  determine  whether  these  organisms  in  a  state  of  apparent 
death  exhibit  any  trace  of  respiratory  exchange,  i.e.  of  absorption 


in  LIVING  MATTER  67 

of  oxygen  and  excretion  of  C0.2.  W.  Kochs  (1892)  used  for  this 
purpose  a  large  quantity  of  perfectly  dry  seeds  of  plants,  which  he 
placed  in  large  glass  tubes  from  which  the  air  had  been  pumped 
out,  and  which  were  then  hermetically  sealed.  After  many 
months,  a  minute  analysis  of  the  contents  of  the  tubes  failed  to 
detect  any  trace  of  carbonic  acid;  and  yet  the  seeds  perfectly 
retained  their  capacity  for  germination.  This  experiment  proves 
that  it  is  possible  to  establish  a  state  of  true  potential  life  in  the 
seeds  of  certain  plants. 

The  results  of  a  number  of  experiments  undertaken  by  the 
author  in  collaboration  with  Piutti  (1888)  on  silk- worm  eggs  were 
somewhat  different.  Without  artificial  desiccation  these  did  not 
entirely  cease  to  breathe  when  kept  for  a  long  while  at  a 
temperature  of  0°  C.,  and  even  at  that  temperature  they  could  not 
survive  prolonged  exposure  to  an  atmosphere  of  pure  nitrogen. 
When  kept  for  139  days  in  conical  flasks  in  which  the  air  was 
maintained  constantly  dry  by  means  of  concentrated  sulphuric 
acid,  they  perished  entirely  if  the  temperature  was  9-14°  0.,  and 
partly  if  it  was  0°  C.  It  is  therefore  clear  that  under  these 
conditions  the  silk-worm  eggs  are  reduced  to  a  state  of  vita 
minima.  When  placed  in  glass  flasks,  in  which  a  perfect  vacuum 
was  produced  by  the  mercury  pump,  after  which  they  were  sealed 
up  and  kept  at  0°  C.,  more  than  half  the  eggs  after  83  days  were 
alive,  and  capable  of  development  when  brought  under  normal 
conditions  of  incubation.  Here  we  have  evidently  a  state  of 
minimal  life  approximating  to  that  of  latent  life.  Lastly,  the 
silk-worm  eggs  were  placed  under  a  glass  bell-jar,  hermetically 
sealed  to  a  plate  and  containing  a  desiccator  with  concentrated 
sulphuric  acid ;  when  after  128  days  the  enclosed  eggs  (which  had 
shrunk  in  an  extraordinary  way  from  the  desiccation)  hatched  out, 
a  very  copious  but  incomplete  brood  of  caterpillars  was  produced, 
which  were  smaller  and  less  lively  than  the  normal.  From  these 
results  it  seems  probable  that  insect  eggs,  like  plant  seeds,  can  be 
artificially  brought  by  desiccation  into  the  state  of  latent  or 
potential  life.  According  to  Preyer's  ingenious  comparison,  this  state 
is  comparable  to  that  of  a  clock  wound  up,  but  with  the  pendulum 
arrested  ;  the  state  of  death,  on  the  contrary,  is  like  a  clock  whicli 
can  no  longer  go  because  its  wheels  are  broken. 

III.  We  saw  in  the  last  chapter  that  plants  breathe  like 
animals,  i.e.  they  take  in  oxygen,  in  order  by  a  slow  process  of 
combustion  to  form  carbonic  acid  and  water.  The  presence  of 
oxygen  is,  accordingly,  one  of  the  most  fundamental  conditions  in 
the  active  upkeep  of  metabolism. 

This  does  not  mean  that  the  presence  of  oxygen  as  such  is 
indispensable  to  the  maintenance  of  life.  In  order  to  under- 
stand its  importance  we  must  start  with  certain  general  con- 
siderations. 


68  PHYSIOLOGY  CHAP. 

Every  assimilatory  or  anabolic  process  results  in  an  accumu- 
lation of  energy,  and  necessarily  implies  a  source  of  kinetic,  which 
can  be  transformed  into  potential,  energy.  Each  dissimilatory  or 
katabolic  process,  on  the  other  hand,  results  in  a  dispersion  of 
energy,  and  presupposes  a  store  of  potential,  to  be  transformed 
into  kinetic,  energy.  This  is  why  the  two  opposite  processes  are 
simultaneous,  or  constantly  and  rapidly  alternating,  during  life, 
while  the  two  together  constitute  metabolism,  which— as  we  have 
seen — is  the  physiological  basis  of  all  the  phenomena  of  life. 

Since  in  green  plants  anabolic  largely  predominate  over 
katabolic  processes,  the  energy  which  they  develop  by  oxidation  is 
inadequate  for  the  synthetic  formation  of  their  highly  complex 
organic  substances,  and  the  intervention  of  the  energy  derived 
from  the  sun's  rays  becomes  necessary. 

In  animals,  on  the  contrary,  in  which  katabolic  processes 
largely  predominate,  the  energy  which  they  develop  by  the 
oxidation  of  organic  substances  is  not  only  enough  to :  yield 
mechanical  work,  and  to  keep  the  temperature  of  the  body  above 
that  of  the  environment,  but  also  suffices  to  secure  the  anabolic 
processes,  or  new  organic  syntheses,  by  elaboration  of  the  food- 
stuffs drawn  from  plants. 

The  destruction  of  the  organic  molecules  by  the  katabolic  pro- 
cesses does  not  take  place  all  at  once,  so  as  immediately  to  turn 
combustible  substances  into  final  products ;  but  it  is  effected 
gradually  and  successively,  the  more  complex  being  converted 
into  other  less  complex  molecules,  and  these  into  the  end-products 
rejected  by  the  body. 

The  presence  of  oxygen  is  not  essential  to  all  these  regressive 
metamorphoses.  In  the  absence  of  free  oxygen,  protoplasm  is  able 
for  a  certain  time  to  obtain  oxygen  from  the  combinations  in 
which  it  is  held  loosely  or  firmly,  and  thus  to  develop  kinetic 
energy.  The  great  plasniodia  of  the  Myxomycetes,  e.g.,  if  placed  in 
a  medium  deprived  of  oxygen,  will  continue  their  movements  for 
three  hours  ;  ciliated  epithelia  can  live  even  longer  without  oxygen 
(Engelmann) ;  excised  frog's  muscle  placed  in  an  atmosphere  of  pure 
hydrogen  will  give  off  carbonic  acid  for  many  hours  before  it 
becomes  inexcitable  (Hermann).  Many  organisms  of  the  lowest 
orders,  particularly  in  the  numerous  groups  of  bacteria,  have  the 
faculty  of  living  permanently  without  oxygen.  Pasteur,  who  was 
the  first  to  call  attention  to  this  most  important  phenomenon,  gave 
the  name  of  anaerobic  to  the  organisms  which  live  in  the  absence  of 
oxygen,  in  contradistinction  from  the  aerobic,  which  can  only 
live  in  presence  of  this  gas.  According  to  Tarozzi  (1905),  the 
incapacity  of  anaerobic  bacteria  to  develop  in  culture  media  in  the 
presence  of  oxygen,  is  due  not  to  a  toxic  action  of  the  oxygen  on 
these  microbes  (as  has  been  stated  by  many  authors)  but  rather  to 
chemical  modifications  of  the  proteins  in  the  broth  used  for  the 


in  LIVING  MATTER  69 

culture.  These  modifications  consist  essentially  in  processes  of 
oxidation,  and  the  anaerobes  appear  to  be  incapable  of  utilising 
highly  oxidised  proteins  in  their  assimilation.  Accordingly,  they 
can  only  develop  when  these  substances  are  once  more  reduced, 
which  is  effected  either  by  artificially  removing  the  oxygen,  or 
(after  Tarozzi)  by  adding  to  the  broth  a  scrap  of  fresh  organ 
aseptically  prepared,  which  acts  as  a  reducer,  in  virtue  of  the 
chemical  processes  of  which  it  is  the  seat,  and  favours  the  develop- 
ment of  the  anaerobes.  In  this  case  it  is  not  necessary  to  remove 
the  oxygen  before  the  bacteria  can  develop.  This  explains  how 
such  development  takes  place  naturally  when  these  bacteria  are  in 
the  presence  of  tissues  of  animals  that  have  just  died,  or,  generally 
speaking,  whenever  they  find  protein  matters  at  their  disposal 
which  have  not  suffered  profound  oxidative  changes.  And  this 
is  why  all  anaerobes  belong  exclusively  to  the  class  of  putrefaction 
microbes  (saprophytes). 

According  to  the  work  of  Duclaux,  Gautier,  and  Ehrlieh, 
anaerobic  metabolism  may  be  recognised  not  only  in  a  great 
number  of  microbes,  but  in  a  still  greater  number  of  plant  and 
animal  cells. 

Many  decompositions  of  organic  molecules  due  to  enzyme  action 
within  the  cell,  or  in  external  secretions,  are  produced  without 
intervention  of  atmospheric  oxygen,  and  are  accompanied  by  a 
development  of  energy  which  is  partly  utilised  by  the  cells  for 
their  constructions  or  organic  syntheses.  Thus,  e.g.,  the  katabolic 
action  of  beer  yeast,  in  the  absence  of  oxygen,  breaks  up  glucose 
into  alcohol  and  carbonic  acid,  with  evolution  of  heat  which  is 
partly  employed  in  the  multiplication  of  the  cells  of  the  ferment. 
In  a  well-aerated  medium  the  same  beer  yeast,  on  the  contrary, 
effects  complete  oxidation  of  the  molecule  of  glucose,  converting  it 
into  water  and  carbonic  acid,  and  in  this  case  there  is  a  greater 
development  of  heat  and  a  far  larger  multiplication  of  Saccliaro- 
myces.  Pasteur's  interpretation  of  these  phenomena  is  very 
illuminating :  Saccharomyces,  in  order  to  nourish  and  reproduce 
itself,  makes  great  use  of  the  energy  developed  in  the  oxidation  of 
sugar,  when  it  is  in  an  oxygenated  medium.  When  oxygen  is 
scarce,  it  utilises  the  inferior  amount  of  energy  which  it  is  able 
to  develop  by  abstracting  oxygen  from  the  fermentable  material, 
i.e.  from  the  same  sugar,  by  a  kind  of  internal  oxidation. 

Accordingly,  it  is  not  oxygen  as  such  that  is  essential  to  life, 
but  the  energy  that  is  developed  by  any  kind  of  oxidation.  Green 
plants  have  less  need  of  oxygen  than  animals,  because  they  obtain 
from  the  sun's  rays  a  great  part  of  the  energy  which  they  require 
in  fixing  the  carbon.  If  the  majority  of  living  beings  positively 
demand  free  oxygen,  it  is  because  much  heat  is  developed  in  its 
combinations,  which  can  be  utilised  in  a  variety  of  ways. 

In  proof  of  the  extent  to  which  oxygen  is  essential  to  the  life 


70  PHYSIOLOGY  CHAP. 

of  the  various  tissues  of  the  higher  animals,  we  may  refer  to  a 
remarkable  experiment  of  Pfliiger's  on  the  frog.  He  placed  two 
of  these  animals  in  an  atmosphere  at  0°  C.  which  had  scrupulously 
been  deprived  of  every  trace  of  oxygen.  After  a  quarter  of  an 
hour  they  exhibited  considerable  dyspnoea,  which,  however,  was 
unaccompanied  with  convulsions.  After  five  hours  the  frogs  were 
quiet  and  flaccid,  but  reacted  to  stimulation  with  a  wire.  After 
nineteen  hours  they  lay  as  if  dead,  and  no  longer  reacted  to  the 
strongest  cutaneous  stimuli,  or  showed  any  trace  of  respiratory 
movement.  After  twenty  hours,  they  were  taken  out  of  their 
prison  into  the  fresh  air,  but  no  sign  of  life  could  be  elicited  in 
spite  of  repeated  insufflation  of  air  through  the  trachea.  On 
opening  the  thorax  of  one  of  the  frogs,  Pfiiiger  was  astonished 
to  see  the  heart  still  beating  with  great  energy,  while  the 
arteries  contained  bright  red  blood.  But  it  was  not  till  two  hours 
after  the  animal  had  been  brought  into  the  oxygenated  atmo- 
sphere that  spontaneous  muscular  movements  were  exhibited, 
followed  by  reflex  movements  and  spontaneous  respiration.  The 
more  complicated  voluntary  movements,  however,  which  depend 
upon  the  higher  nervous  system  never  came  back. 

To  explain  this  long  survival  in  an  atmosphere  wholly  deprived 
of  oxygen,  it  must  be  admitted  for  vertebrates  also  that  the  living 
protoplasm  of  the  various  tissues  has  the  property  (in  different 
degrees)  of  utilising  the  oxygen  which  is  bound  up  in  the 
organic  molecules.  The  cells  of  the  central  nervous  system 
are  the  most  sensitive  to  deprivation  of  free  oxygen ;  other  cells, 
on  the  contrary,  can  live  for  a  long  while  in  a  medium  destitute  of 
oxygen,  because  they  have  the  power  of  taking  it  from  organic 
combinations,  and  utilising  the  potential  energy. 

The  most  interesting  phenomenon,  from  the  point  of  view  of 
anaerobic  metabolism,  is  afforded  by  the  group  of  bacteria  which 
are  not  only  capable  of  living  in  the  absence  of  oxygen,  but  die 
in  a  medium  that  contains  it,  e.g.  Tetanus  and  Anthrax  bacilli. 
Interesting  phenomena,  too,  are  exhibited  by  other  bacteria,  e.g. 
the  comma  bacillus  of  Cholera,  which  is  greedy  of  oxygen,  and  is 
at  the  same  time  capable  of  living  and  multiplying  enormously 
in  the  intestine,  where  there  is  no  trace  of  free  oxygen,  so  that  it 
must  necessarily  utilise  the  combined  oxygen  of  the  alkaline  salts. 

IV.  In  addition  to  food -stuffs,  water  and  oxygen,  which 
penetrate  into  the  body,  and  directly  condition  metabolism, 
other  conditions  of  a  dynamic  character  are  indispensable 
in  order  that  the  vital  functions  may  be  accomplished.  The 
external  temperature  exercises  a  predominant  influence  on  elemen- 
tary organisms.  Each  cell  demands  a  temperature  oscillating 
between  given  limits,  beyond  which  the  cell  must  die.  For  the 
majority  of  plant  and  animal  cells,  the  maximal  limit  of  endurable 
temperature  lies  between  40°  and  47°  C.  Kiihne  found  that  the 


in  LIVING  MATTER  *7l 

contractile  protoplasm  of  Amoebae  coagulated  sometimes  at  40°  C., 
sometimes  at  45°  C.  For  plant  cells,  Max  Schultze  found  that  the 
fatal  temperature  could  be  raised  to  47°  C.  Other  elementary 
organisms,  indeed,  support  much  higher  temperatures,  which  would 
seem  incredible  if  they  were  not  substantiated  by  direct  measure- 
ment. In  the  hot  baths  of  Casamicciola,  e.g.,  certain  Algae  nourish 
at  a  temperature  of  63°  C.,  while,  according  to  Ehrenberg,  some 
of  the  ciliated  Infusoria  (Occillaria  or  Eotifera)  can  live  at  a 
temperature  of  81°  -  85°  C.  More  surprising  still,  the  spores 
of  Anthrax,  according  to  Koch,  Brefeld  and  others,  can  support  a 
temperature  of  over  100°  C.,  and  only  lose  their  vitality  completely 
after  three  hours'  dry  heat  at  140°  C.  It  must  be  remembered  in 
explanation  that  the  protoplasm  of  these  organisms  consists  of 
proteins  combined  in  such  a  way  that  they  do  not  coagulate  nor 
decompose  at  these  high  temperatures. 

The  minimum  temperature  compatible  with  life  is  equally 
surprising.  While  as  a  rule  the  poikilothermic  animals  and  plants 
die  when  the  temperature  falls  to  such  a  point  that  the  water 
imbibed  by  the  protoplasm  freezes,  Raoul  Pictet's  latest  experi- 
ments show  that  a  temperature  of  less  than  0°  C.  is  not  necessarily 
fatal  to  certain  organisms.  In  fact  he  ascertained  positively  that 
fishes  frozen  at  a  temperature  of  -  15°  C.  can  recover  their  vitality, 
provided  the  thawing  is  effected  with  great  caution.  If,  however, 
the  fall  in  temperature  amounts  to  -  20°  C.,  they  inevitably  perish. 
Frogs,  on  the  contrary,  tolerate  a  temperature  of  -  28°  C.,  centipedes 
one  of  -  50°  C.,  while,  lastly,  bacteria  can  survive  exposure  to 
- 100°  C. 

Here  we  reach  the  vexed  question  whether  frozen  animals, 
capable  of  recovering  their  vitality  on  thawing,  are  in  a  state  of 
minimal  or  of  absolute  latent  vitality.  Although  the  latter 
possibility  is  not  excluded,  Pictet's  experiments  do  not  seem  to 
favour  this  hypothesis.  If  these  frozen  fishes  were  in  a  condition 
of  latent  vitality,  it  is  difficult  to  see  why  they  should  not  be 
indifferent  to  a  fall  of  temperature  below  -  15°  C.,  which  they  can 
survive.  It  seems  more  rational  to  admit  that  at  this  temperature 
metabolic  exchanges  are  still  maintained,  although  reduced  to  the 
lowest  terms,  and  that  death  ensues  when  metabolism  ceases 
altogether. 

V.  The  pressure  of  the  air  and  water  in  which  these  organisms 
live  must  also  be  considered  among  the  general  conditions  of  life. 
It  is  indeed  evident  a  priori  that  pressure  must  act  against  the 
thermal  vibrations  of  the  atoms  ;  when  therefore  there  is  a  marked 
rise  of  pressure  obstructing  the  thermal  vibrations,  this  favours 
the  appearance  of  chemical  combinations,  while  a  marked  diminu- 
tion, by  increasing  the  amplitude  of  the  said  vibrations,  must 
weaken  the  mutual  attraction  of  the  atoms  and  dissociate  the 
unstable  chemical  combinations. 


72  PHYSIOLOGY  CHAP. 

Very  little  work  has  been  done  on  the  determination  of  the 
limits  between  which  the  total  pressure  of  the  air  and  water,  and 
the  partial  pressure  of  the  oxygen  and  carbonic  acid  which  these 
contain,  condition  the  life  of  the  organisms  which  inhabit  them. 

The  experiments  of  Paul  Bert  (1873)  bring  out  the  interesting 
fact  that  pure  oxygen  under  a  pressure  of  three  atmospheres  is 
fatal  to  warm-blooded  animals,  while  ordinary  air  only  produces 
the  same  effect  at  a  pressure  of  15-20  atmospheres.  The  same 
fatal  effect  ensues  when  the  partial  pressure  of  the  oxygen  of  the 
air  is  reduced  below  a  certain  limit. 

In  order  to  determine  how  great  a  fall  in  the  barometric 
pressure  is  compatible  with  life,  we  may  utilise  certain  data 
furnished  not  so  much  by  ascents  of  the  highest  mountains  as 
from  aerostatic  ascents,  in  which  the  effects  of  fall  of  barometric 
pressure  are  not  complicated  by  muscular  fatigue.  The  famous 
ascent  by  Croce-Spinelli,  Sivel,  and  Tissandier  in  1875  was  fatal 
to  the  two  former.  When  the  balloon  reached  8000  metres 
Tissandier,  the  sole  survivor,  lost  consciousness,  and  only  came  to 
his  senses  when  the  balloon  had  dropped  to  7059  metres. 

We  know  hardly  anything  of  the  effect  of  aqueous  pressures 
upon  sea  animals.  Contrary  to  former  conceptions,  it  has  within 
the  last  few  decades  been  ascertained  that  there  exists  a  special 
flora  and  fauna  at  the  lowest  depths  of  the  ocean,  in  regions  where 
there  is  a  pressure  of  several  hundred  atmospheres,  and  where  no 
light  can  ever  penetrate.  The  fishes  caught  at  the  greatest 
depths  are,  when  first  brought  to  the  surface,  so  distended  in 
consequence  of  the  sudden  reduction  of  pressure,  which  allows  the 
gases  in  their  bladder  to  expand,  that  the  viscera  protrude  from 
their  mouths  and  the  scales  stand  up  (Keller). 

In  regard  to  the  pressure  exerted  by  water  upon  marine 
animals,  the  fact  must  be  insisted  on  that  it  exercises  a  great 
influence  only  upon  such  organs  as,  like  the  fish's  swim-bladder, 
contain  gas  in  the  gaseous  state,  and  do  not  communicate  with  the 
exterior.  The  tissues  of  these  animals,  which  may  be  considered 
as  liquids,  only  feel  the  effects  of  the  high  pressure  in  a  negligible 
degree,  since,  as  we  know  from  physics,  several  hundredths  of 
atmospheric  pressure  are  necessary  in  order  to  obtain  any  marked 
diminution  in  volume  of  fluids — these  being  practically  incom- 
pressible. This  is  confirmed  by  the  fact  that  marine  animals,  such 
as  Echinoderms,  Molluscs,  Crabs,  and  Selachians  or  Teleosteans, 
which  have  no  swim-bladder,  and  normally  live  at  a  great  pelagic 
depth,  can  be  transported  to  the  surface  without  any  danger,  and 
continue  to  live  for  a  long  time  in  ordinary  aquaria  when  the 
pressure  of  the  water  is  from  |-1  metre. 

VI.  With  the  exception  of  those  above  enumerated,  none  of 
the  general  external  conditions  are  essential  to  life.  Other 
external  physical  or  chemical  factors  may  indeed  influence  vital 


JH  LIVING  MATTEE  73 

metabolism  to  such  a  marked  degree  so  as  to  render  them 
indispensable  to  the  life  of  given  groups  of  organisms,  e.g.  light  in 
the  case  of  green  plants.  These  special  external  conditions  are 
usually  known  as  stimuli,  since  they  exert  a  direct  influence  on 
the  excitability  of  the  protoplasm  as  expressed  in  the  various 
forms  of  excitation. 

In  the  previous  chapter  we  distinguished  between  automatic 
and  reflex  excitation ;  the  former  being  determined  by  internal, 
the  latter  by  external  stimuli.  This  must  not  be  understood  to 
mean  that  the  excitations  which  have  the  character  of  spontaneity, 
as,  opposed  to  the  reflexes  provoked  from  without,  are  independent 
of  all  external  determining  factors.  The  first,  like  the  second,  are 
effected  under  the  constant  influence  of  the  general  and  normal 
external  conditions  of  life  ;  but  while  automatic  excitations  have 
for  their  immediate  and  determining  cause  a  stimulus  or  impulse 
proceeding  from  the  living  matter  itself,  reflex  excitations  have 
for  their  immediate  and  determining  cause  either  a  sudden  change 
in  the  normal  external  conditions,  or  the  abrupt  and  unexpected 
intervention  of  other  special  external  agents. 

The  external  agents  that  commonly  function  as  stimuli  are 
represented  by  different  chemical  actions,  by  various  mechanical 
shocks,  by  light,  heat,  and  electricity. 

The  changes  in  metabolism  determined  by  the  action  of 
stimulating  agents  may  be  predominatingly  anabolic  or  katabolic 
in  character.  In  the  first  case  there  is  development  of  kinetic 
energy,  and  the  phenomena  are  those  of-  excitation  properly  so- 
called  ;  in  the  second,  there  is  an  accumulation  of  potential  energy, 
and  the  phenomena  are  said  to  be  assimilatory.  or  trophic,  or 
inhibitory,  according  to  the  most  conspicuous  characteristic  which 
they  present  under  observation. 

When  the  action  of  the  stimuli  is  too  prolonged,  or  too  frequently 
repeated,  or  exceeds  the  physiological  limits  in  its  intensity, 
there  may  result  not  an  increase  but  a  depression,  suspension,  or 
abolition  of  metabolism,  as  exhibited  in  the  phenomena  of  fatigue, 
paralysis,  or  death  of  the  protoplasm. 

We  must  now  briefly  summarise  the  most  universal  and  best 
ascertained  conclusions  in  each  of  these  categories  of  phenomena. 

VII.  Innumerable  chemical  compounds  function  as  stimuli 
when  brought  into  relation  with  living  matter,  i.e.  they  provoke 
phenomena  of  excitation.  The  mode  in  which  they  act  has,  how- 
ever, been  experimentally  studied  only  in  a  very  few  cases.  We 
must  therefore  confine  ourselves  to  recording  certain  typical 
phenomena  which  are  particularly  worthy  of  attention. 

Max  Schultze  (1863)  and  Kiihne  (1864)  made  classical  re- 
searches on  the  effect  of  chemical  stimuli  upon  the  amoeboid 
movements  of  masses  of  naked  protoplasm,  such  as  the  Rhizopoda 
(Amoebae,  Myxomycetes,  Polythalamidae,  etc.).  The  effect  most 


74 


PHYSIOLOGY 


CHAP. 


generally  observed  was  contraction,  i.e.  retraction  of  the  pseudo- 
podia.  The  most  various  chemical  substances  are  capable  of 
producing  this  effect :  1-2  per  cent  solution  of  sodium  chloride, 
dilute  hydrochloric  acid  O'l  per  cent,  caustic  potash  1  per  cent, 
weak  solutions  of  other  acids,  alkalies,  or  salts. 

The  Ehizopods  treated  with  these  solutions  assume  a  globular 
form  on  retracting  their  pseudopodia,  owing  to  the  concentric 
contraction  of  the  protoplasm  (Fig.  18).  Ciliated  cells,  on  the 
contrary,  when  treated  with  the  same  stimuli,  increase  their 
vibratile  movements — sometimes  to  a  very  marked  extent.  Smooth 
and  striated  muscles  contract,  and  sometimes  exhibit  a  rhythm  of 
contraction  that  they  do  not  normally  possess,  recalling  the 
rhythmical  movements  of  the  vibratile  cilia. 

Besides  the  contractile  effects  of  chemical  stimulation,  it  is 


FHJ.  is. — Actinosphaerimn  Eichhornii.  (Venvorn.)  a,  under  normal  conditions  ;  h,  at  commence^ 
ment  of  chemical  excitation,  the  filiform  pseudopodia  are  contracted  and  varicose ;  <;,  after 
prolonged  chemical  excitation,  the  pseudopodia  are  completely  retracted. 

possible  also  to  observe  expansive  effects,  i.e.  active  elongation  of 
the  pseudopodia  in  Amoebae,  Myxomycetes,  etc.,  effects  which  in  the 
first  instance  were  studied  by  Kiihne.  On  placing  an  amoeba,  for 
instance,  in  a  gas  chamber  in  which  oxygen  has  been  substituted 
for  hydrogen,  the  movements  are  suspended  after  a  short  time. 
On  again  admitting  oxygen,  the  amoebae,  after  twenty-four  hours 
of  inactivity,  at  once  begin  to  expand  their  pseudopodia  with 
normal  vivacity. 

Even  more  important  than  this  direct  excitation  are  the 
phenomena  of  the  directive  action  of  chemical  stimuli  upon  the 
movements  of  elementary  organisms,  phenomena  known  as  chemo- 
tactic  or  chemotropic.  Chemotaxis,  as  first  discovered  by  Engelniann 
on  Bacteria,  observed  by  Stahl  on  Myxomycetes,  and  studied  on  a 
large  scale  by  the  botanist  Pfeffer  in  1887,  has  assumed  a  great 
importance. 

Positive  must  be  distinguished  from  negative  chemotaxis.     The 


in 


LIVING  MATTER 


former  consists  in  the  active  approach  of  the  micro-organisms  to 
the  source  of  the  chemical  stimulus,  as  if  attracted  by  it ;  the 
second  consists  in  the  opposite  phenom- 
enon, i.e.  active  withdrawal  from  the  seat 
of  the  stimulus,  as  if  it  exerted  some 
repulsive  action. 

A  given  solution  may  be  an  energetic 
chemotactic  stimulus  for  one  organism, 
and  weak  'for  another.  The  efficiency  of 
the  stimulus  depends  on  its  chemical 
constitution ;  potash,  e.g.,  is  active  in 
combination  with  one  acid  and  not  with 
another.  Certain  poisons  (sodium  salicyl- 
ate,  morphia)  in  weak  solutions  exert  an 
attractive  action,  in  concentrated  forms 
a  repulsive  action.  Some  substances 
(alcohol,  alkalies,  free  acids)  always  have 
a  repellent  action,  i.e.  they  exert  negative 
chemotaxis. 

The  method  adopted  by  Pfeffer  in 
studying  chemotaxis  is  very  simple :  he 
merely  immerses  in  the  water  which  con- 
tains the  microbes  a  capillary  glass  tube 
filled  with  the  solution  to  be  investigated, 
and  closed  at  one  end.  If  the  microbes 
penetrate  into  the  tube,  there  is  positive 
chemotaxis  ;  if  they  move  away,  there  is 
negative  chemotaxis.  If,  e.g.,  a  O'Oo  per 
cent  solution  of  malic  acid  is  introduced 
into  the  capillary  tube,  the  open  end  of 
which  dips  into  a  drop  of  fluid  containing 
the  spermatozoids  of  Ferns,  the  malic  acid 
will  scarcely  have  begun  to  diffuse  in  the 
drop  when  the  spermatozoids  move  towards 
the  entrance  of  the  tube  and  crowd  into 
it.  The  same  thing  may  be  seen  with  a 
much  weaker  solution  (O'OOl  per  cent)  of 
malic  acid.  The  movements  of  the  sper- 
matozoids must  be  directed  by  the  differ- 
ence in  concentration  of  the  acid  which 
is  in  contact  with  the  different  parts  of 
their  body.  When  the  concentration  of 
the  acid  diffused  in  the  drop  becomes  the 
same  at  every  point,  it  can  no  longer 

exercise  any  directive  action  upon  the  movements  of  the  sper- 
matozoids. 

Leber,  Massart  and  Bordet,  Metschnikoff  and  others  discovered 


FIG.  19.  —  Positive  cliemotaxis  of 
leucocytes  in  presence  of  Maphy- 
lococcu&pyogenes  allius.  (Massart. ) 
Capillary  glass  tube  (magnified 
under  the  microscope),  closed 
at  one  end,  and  tilled  with  a 
culture  of  Staphylococcus,  to- 
wards which  the  leucocytes 
are  streaming  through  the  open 
end  of  the  tube.  The  observa- 
tion is  made  after  the  capil- 
lary tube  has  been  introduced 
into  the  peritoneal  cavity  of 
the  frog,  or  beneath  the  skin  of 
a  rabbit,  and  kept  there  10-12 
hours. 


76  PHYSIOLOGY  CHAP. 

chemotactic  activity  in  the  leucocytes  of  vertebrate  blood.  The 
products  of  the  metabolism  of  pathogenic  bacteria  exert  a  marked 
•chemotactic  action  upon  them  (Fig.  19),  a  fact  which  is  of  great 
importance  in  the  interpretation  of  the  inflammatory  phenomena 
of  infective  diseases,  as  we  shall  see  in  discussing  Blood. 

VIII.  Mechanical  stimuli  (blow,  contact,  puncture,  shake, 
pressure,  etc.)  are  the  simplest  means  of  provoking  excitation 
in  living  matter.  The  least  shake  of  the  object-carrier  on  which 
the  movements  of  an  amoeba  are  being  watched  under  the 
microscope  is  sufficient  to  produce  temporary  standstill,  and  if  the 
impact  is  strong  enough  a  partial  retraction  of  the  pseudopodia. 
If  the  shock  is  repeated  at  frequent  intervals  the  effects  induced 
by  each  stimulus  summate,  resulting  after  a  minute  or  two  in  a 
true  mechanical  tetanus,  during  which  there  is  a  concentric 
•contraction  of  the  whole  of  the  protoplasm,  which  causes  the 
amoeba  to  assume  a  globular  form. 

In  addition  to  general  mechanical  stimulation,  the  effects  of  local 
stimulation  have  been  experimentally  studied,  by  touching  or  stab- 
bing the  amoeba  with  a  blunt  body  or  with  very  fine  needles.  In  this 
case,  when  a  reaction  appears,  it  is  at  first  confined  to  the  point 
stimulated,  whence  it  is  slowly  transmitted  to  the  rest  of  the  body. 

The  mechanical  excitations  of  the  living  matter  consist 
for  the  most  part  in  a  modification  of  the  pressure  relations 
under  which  it  exists.  In  every  case  in  which  there  is  a 
difference  of  pressure  at  two  different  parts  of  the  body  of  any 
organism,  phenomena  of  excitation  are  manifested,  which,  since 
they  are  produced  by  a  unilateral  pressure,  are  known  as  barotactic. 
Several  forms  of  barotaxis  may  be  distinguished  according  to  the 
kind  of  pressure,  while  it  also  can  be  positive  or  negative,  according 
-as  the  organism  turns  towards  the  side  of  greater  or  less  pressure. 

Verworn  groups  under  the  name  of  thigmotaxis  the  tendencies 
exhibited  by  many  organisms,  both  animal  and  vegetable,  to 
adhere  to  the  surface  of  more  solid  bodies,  or  to  penetrate  through 
their  pores,  even  in  defiance  of  gravity. 

Stahl  defines  as  rheotaxis  the  peculiarity  certain  organisms 
exhibit  of  moving  in  the  direction  contrary  to  a  current  of  water. 
Since  this  movement  is  determined  by  pressure  acting  in  a  particular 
way,  rheotaxis  is  merely  a  special  form  of  positive  barotaxis. 
Thus  far  the  phenomenon  has  been  studied  only  in  the  plasmodia 
of  Myxomycetes  and  in  a  few  plants ;  but  it  is  highly  probable  that 
the  rise  of  the  spermatozoa  in  animals  and  man  from  the  vagina 
to  the  uterus,  and  thence  to  the  oviduct  to  meet  the  ovum,  is  a 
rheotactic  phenomenon,  since  this  movement  is  accomplished  in  a 
direction  contrary  to  that  of  the  current  of  mucous  fluid  set  up  by 
the  cilia  of  the  epithelial  cells  which  line  the  surface  of  the  uterus, 
and  which  vibrate  in  a  direction  contrary  to  the  movements  of  the 
spermatozoa. 


Ill 


LIVING  MATTER 


A  third  form  of  barotaxis  is  geotaxis,  or  the  well-known 
property  of  plants  to  place  themselves  with  their  median  axis  in  a 
definite  direction  toward  the  centre  of  the  earth.  The  stimulus  in 
this  case  is  afforded  by  minimal  differences  of  pressure  acting  on 
points  at  different  heights  of  the  organism.  The  stems  of  trees 
grow  away  from  the  centre  of  the  earth,  and  are,  therefore, 
negatively  geotactic;  the  roots  grow  toward  the  centre  of  the 
earth,  and  are,  therefore,  positively  geotactic  ;  further,  the  leaves, 
and  not  seldom  the  branches,  grow  in  a  direction  tangential  to  the 
earth's  surface,  and  thus  exhibit  transverse  geotaxis. 

.  Loeb  (1888)  discovered  that  geotaxis  is  a  phenomenon  widely 
diffused  among  animals  also.  It  is  possible  to  convert  animals 
that  exhibit  negative,  into  animals  ex- 
hibiting positive,  geotaxis,  and  vice  versa. 

Many  infusoria  and  bacteria  exhibit 
geotactic  phenomena.  They  frequently 
collect  on  the  surface  of  the  water  in 
which  they  live  (negative  geotaxis,  Fig. 
20) ;  at  other  times  they  sink  down  and 
crowd  together  at  the  bottom  (positive 
geotaxis). 

Knight  (1809)  showed  that  geotactic 
phenomena  are  determined  by  differences 
in  pressure  acting  like  gravity  on  the 
different  points  of  the  vegetable  organ- 
ism. He  employed  wheels  turning  in 
a  vertical  plane,  to  which  he  attached 
plants  in  various  positions,  as  well  as 
germinating  seeds.  He  found  that  all 
the  stems  grew  in  towards  the  centre 
of  the  wheel,  while  the  roots  grew  away 
from  it.  Jensen  practically  repeated  the 
same  experiments  on  infusoria  living  at  the  surface  of  the  water, 
by  rotating  the  test  tubes  which  contained  them  in  the  centrifuge. 
Provided  this  were  not  driven  too  quickly,  so  as  to  make  the 
infusoria,  which  are  specifically  heavier  bodies,  drop  to  the  bottom 
of  the  test  tube,  they  remained  at  the  top,  where  pressure  is  lowest 
during  rotation. 

IX.  Heat  rarely  exerts  any  direct  stimulating  action  on  living 
matter.  In  the  higher  animals,  however,  the  special  terminal 
organs  of  certain  centripetal  nerve-fibres  are  excited  by  heat. 
Kuhne  was  the  first  to  observe  thermal  tetanus  in  Amoebae 
when  the  temperature  was  raised  to  35°  C.  On  cooling  the 
atmosphere  again,  the  amoeboid  movements  were  slowly  restored ; 
heating  to  40-45°  C.  kills  the  animal  by  coagulation  of  its  proto- 
plasm. 

When  the   heat  acts  on  one  part   only  of  the  amoeba,  the 


FIG.  20. — Glass  tube  containing  Para- 
moecia.  (Jensen.)  In  consequence 
of  negative  geotaxis,  the  infusoria 
have  collected  at  the  top  of  the 
tube,  although  they  are  specifically 
heavier  than  the  fluid. 


78  PHYSIOLOGY  CHAP. 

stimulus  is  found  capable  not  merely  of  exciting  protoplasmic 
movements,  but  even  of  determining  their  direction  up  to  a  certain 
point.  Verworn  observed  that  amoebae  always  move  in  a  direction 
opposite  to  the  thermal  stimulus,  i.e.  they  exhibit  negative 
thermotaxis.  Mendelssohn  studied  on  a  ciliated  infusorium// 
Paramoecium,  the  thermotactic  influence  of  different  grades  of 
temperature.  When  one  end  of  a  vessel  full  of  liquid,  and 
swarming  with  Paramoecia,  is  heated  to  24-28°  C.,  the  creatures 
move  to  the  cooler  end  of  the  vessel ;  when,  on  the  contrary,  one 
end  of  the  vessel  is  cooled  below  the  said  degrees,  the  infusoria 
move  towards  the  warmer  end.  Thus  there  may  be  positive  or 
negative  thermotaxis  according  to  the  degree  of  temperature. 

In  this  case,  as  in  cherno-  and  barotaxis,  the  movement  are 
determined  by  the  difference  of  temperature  at  the  two  poles  of 
the  Paramoecium,  differences  which  can  be  estimated  at  about 
0-01°  C. 

X.  Light  rays,  like  heat  rays,  act  as  a  direct  stimulus  on 
comparatively  few  elementary  organisms.  In  the  higher  animals 
they  only  affect  the  nervous  elements  of  the  retina,  and  great 
intensity  is  required  to  stimulate  the  cutaneous  -endings  of  the 
thermal  nerves  as  well.  The  skin  of  invertebrates  is  also  excitable 
to  light. 

Many  observations  have  been  made  in  order  to  determine  the 
nature  of  the  action  of  light  upon  Protista,  and  to  ascertain 
whether  excitability  to  light  is  a  general  property  of  protoplasm, 
or  first  appears  during  the  phylogenic  evolution  of  living  beings. 
The  results  with  amoebae  were  purely  negative.  Other  Khizopoda, 
however,  were  seen  to  contract  on  sudden  illumination. 

E.  Oehl  (1886-91)  saw  that  the  leucocytes  of  the  blood  both  of 
man  and  frog,  when  exposed  to  bright  sunshine  under  the 
microscope,  reacted  by  active  migratory  and  amoeboid  movements, 
which  were  not  present  previous  to  the  photic  stimulation. 

The  work  of  Strasburger  and  others  shows  that  intensity  of 
light  exerts  a  great  influence  on  bacteria  and  diatoms,  so  that  up 
to  a  certain  point  of  intensity  they  exhibit  positive  phototaxis, 
and  approach  the  source  of  light ;  with  greater  intensity  they 
move  farther  off,  and  exhibit  negative  phototaxis ;  at  a  mid-point 
they  show  themselves  wholly  indifferent.  The  wave-length  of  the 
light  rays  is  also  of  great  importance.  Engelmann  has  shown 
that  the  Bacterium  photometricum  (observed  in  the  micro- 
spectroscope)  swarms  into  the  region  of  the  ultra-red  rays,  and  to 
a  less  extent  into  that  of  the  orange  and  yellow  rays,  i.e.  towards 
Frauenhofer's  D-line  (Fig.  21). 

The  term  heliotaxis  has  long  been  employed  to  denote  the 
common  property  of  plants  to  turn  on  their  axis  in  the  direction 
-of  the  sun's  rays.  The  phenomenon  is  particularly  conspicuous 
in  plants  grown  inside  the  house.  Both  stems  and  petioles  curve 


Ill 


LIVING  MATTEE 


towards  the  light  that  conies  in  at  the  windows  (positive  heliotaxis), 
while  the  surfaces  of  the  leaves  spread  out  perpendicularly  in  the 
direction  of  the  light  rays  (transverse  heliotaxis).  In  plants  with 
aerial  roots  these  turn  and  grow  towards  the  darkest  part  of  the 
room  (negative  heliotaxis). 


FIG.  21. — Bacterium  photometrii'iim,  in  micro-spectroscope.     (Engehnanii.)    The  bacteria 
are  collected  in  the  region  of  the  ultra-red  and  yellow  rays. 

Heliotactic  movements  are  especially  favoured  by  the  blue  and 
violet  rays ;  red  and  yellow  rays  are  practically  inactive  (Fig.  22). 

Loeb  (1888)  described  phenomena  of  heliotaxis  in  many 
animals,  which  are  perfectly  comparable  with  those  observed  on 
plants ;  they  are  also  determined  by  the  most  refrangible  rays  of 
the  spectrum.  The  mechanical  explanation  of  the  phenomenon  is, 
according  to  Loeb,  that  the  symmetrical  points  of  an  organism 


FIG.  22. — (lalium,  aparina  showing  heliotaxis.     (Noll.)    The  plant  curves  left  or  light,  to  the 
source  of  light,  as  indicated  by  the  arrow  L.     The  leaves  exhibit  transverse  heliotaxis. 

possess  equal  excitability,  and  the  unsynimetrical  points  unequal 
excitability ;  the  points  nearest  the  buccal  pole  possess  an  excit- 
ability greater  than,  or  different  in  form  from,  that  of  the  points 
nearest  the  opposite  pole.  By  this  is  meant  that  with  unilateral 
illumination  the  muscles  of  the  excited  side  are  thrown  into  a 
tension  which  is  relatively  greater  or  less  than  that  of  the  muscles 
of  the  opposite  side,  so  that  the  animal  deviates  in  the  direction  of 
its  movements,  in  the  sense  of  positive  or  negative  heliotaxis.  In 


80  PHYSIOLOGY  CHAP. 

some  animals  it  is  possible  to  transform  positive  into  negative 
heliotaxis,  and  vice  versa. 

XL  Electrical  stimuli  are  those  most  frequently  adopted  by 
physiologists  for  the  excitation  of  living  matter.  Their  action  on 
muscle  and  nerve  will  be  treated  at  length  in  another  connection. 
Here  we  must  confine  ourselves  to  the  effects  of  electrical  excitation 
on  unicellular  organisms. 

Kiihne  and  Engelmann  were  the  first  who  investigated  this 
subject.  They  both  found  that  after  weak  induction  shocks  the 
amoebae  suspended  their  locomotor  movements;  with  stronger 
shocks  the  pseudopodia  assume  a  globular  form ;  if  the  shocks  were 
still  further  strengthened,  electrical  tetanus  resulted,  followed  by 
a  kind  of  coagulation  of  the  protoplasm,  which  was  shared  by  the 
nucleus.  Galvanic  currents  also,  in  proportion  with  their  intensity, 


FIG.  '23. — Kathodic  galvanotaxis  in  a  drop  of  water  with  paramoecia.  (Verworn.)  c,  on  closure 
of  current,  the  paramoecia  swim  in  curved  lines  to  approach  the  kathode ;  l>,  paramoecia 
collected  round  the  kathode. 

produced   a   partial   or   total   contraction    of   the   protoplasm   of 
amoebae. 

Verworn  discovered  a  directive  action  of  the  galvanic  current 
analogous  to  that  produced  by  other  stimuli,  which  he  terms 
galvanotaxis.  He  particularly  investigated  certain  species  of 
ciliated  infusoria,  e.g.  Paramoecia.  When  immersed  in  a  drop  of 
water  through  whicli  current  is  passing,  these  infusoria  flock  to 
the  kathode  in  wavy  movements  which  are  more  pronounced  in 
proportion  as  the  current  is  weaker.  On  breaking  the  circuit  the 
Paramoecia  scatter  themselves  again  uniformly  through  the  drop 
of  water  (Fig.  23).  This  is  not  a  case  of  kataphoric  action,  i.e.  of 
mechanical  transport  in  the  direction  of  the  current,  such  as  might 
occur  with  non-living  particles,  because  the  infusoria  would  then 
swim  in  a  straight  line,  and  move  more  rapidly,  with  no  orientation 
of  the  principal  axis  of  the  body.  Moreover,  chloroform  or  ether 
paralyse  these  movements,  which  would  not  occur  if  they  did  not 
represent  physiological  phenomena  in  living  beings.  Budgett  and 
Loeb  noted  that  these  same  Paramoecia  moved  to  the  anode  if  the 
water  which  contains  them  is  replaced  by  a  0*4-0*7  per  cent 
solution  of  sodium  chloride. 


in  LIVING  MATTER  81 

Dineur  found  that  the  leucocytes  of  the  blood  also  exhibit 
galvanotactic  properties  with  a  marked  preference  for  the  anode. 

A  different  form  of  kathodic  and  anodic  galvanotaxis  was 
observed  at  the  end  of  1885  by  Hermann.  When  a  galvanic 
current  is  passed  through  a  vessel  containing  tadpoles  or  fish 
embryos,  these  animalcules  orientate  themselves  with'  their  long 
axes  in  the  direction  of  the  lines  of  current  so  that  the  head  faces 
the  anode  and  the  tail  the  kathode.  They  remain  in  this 
position  as  long  as  current  is  passing ;  if  its  direction  be  reversed, 
they  face  to  the  opposite  direction,  like  soldiers  at  the  word  of 
command. 

Verworn  recognised  another  form  of  galvanotaxis  in  a  ciliated 
infusorium,  Spirostomum  amliguum,  which,  when  traversed  by  the 
galvanic  current,  turns  so  that  the  principal  axis  of  its  body  is 
at  right  angles  to  the  direction  of  the  current.  This  he  terms 
transverse  galvanotaxis. 

XII.  The  directive  action  of  stimuli,  particularly  of  those  due 
to  light  and  temperature,  is  of  special  importance  for  marine 
organisms.  Scientific  data  in  regard  to  the  fauna  and  flora  of  the 
ocean  are  at  present  scanty  in  comparison  with  our  knowledge  of 
the  terrestrial  fauna  and  flora,  but  there  seems  reason  to  believe 
that  the  variety  and  magnitude  of  the  animal  and  vegetable 
kingdoms  of  the  ocean  are  incomparably  greater  than  of  those 
upon  the  earth.  The  paucity  of  data  in  regard  to  life  in  the  deep 
sea  is  obviously  due  to  the  difficulty  of  securing  such  beings  as 
live  at  a  depth  of  several  thousand  metres  below  the  surface. 

Many  expeditions  have  been  organised  for  the  purpose  of 
studying  marine  biology;  these  are  equipped  with  ponderous 
dredges,  and  are  intended  to  remain  several  months  at  sea  in  order 
to  collect  with  different  kinds  of  apparatus,  at  various  seasons  of 
the  year,  the  organisms  that  exist  at  different  levels  or  at  the 
bottom  of  the  ocean.  The  most  important  have  been  the  Challenger 
Expedition,  conducted  by  Murray  and  Thompson  (1884),  and  the 
Valdivia,  conducted  by  Chun  (1898-99),  in  different  seas.  In  the 
Mediterranean,  Krupp,  on  the  Maia  and  the  Puritan,  investigated 
the  pelagic  fishes,  the  scientific  results  of  this  expedition  having 
been  illustrated  and  published  by  S.  Lo  Bianco  (1901-3). 

The  distribution  of  organisms  in  the  different  strata  of  water 
(bathymetric  distribution,  either  in  the  vertical  or  the  horizontal 
direction)  has  been  determined  with  a  fair  amount  of  accuracy 
by  the  use  of  special  contrivances,  constructed  ad  hoc.  Such 
are  the  nets  fitted  with  an  apparatus  enabling  them  to  be  closed 
at  any  required  depth  (measured  by  the  soundings),  so  that  they 
cannot,  when  pulled  up  through  the  supernatant  strata  of  water, 
enclose  any  animals  from  these  higher  levels.  Some  are  draw-nets 
weighted  with  heavy  rings  of  iron  or  other  metal,  which  fall  to  the 
bottom  and  are  pushed  along,  gathering  up  the  living  organisms 

VOL.  I  G 


82  PHYSIOLOGY  CHAP. 

from  the  ocean  bed.  By  this  method  a  certain  amount  of  exact 
knowledge  has  been  obtained  in  regard  to  the  fauna  and  flora  of 
the  seas.  As  regards  the  vertical  distribution  of  these  pelagic 
organisms,  it  is  interesting  to  note  that  the  forms  which  live  at 
different  heights  in  the  same  region  of  the  sea  vary  enormously 
among  themselves,  so  that  we  ought  to  speak  of  so  many  special 
biological  zones  in  relation  to  the  different  depths  of  water. 

The  main  factor  which  determines  this  diversity  in  the  forms 
of  life  at  various  depths,  is  light ;  then  come  temperature,  and 
movement  of  the  water,  which  are  of  secondary  importance ;  while 
pressure  of  water  is,  save  for  the  Teleosteans  provided  with  a  swim- 
bladder,  of  no  importance,  as  we  have  already  pointed  out. 

In  regard  to  light,  the  following  zones  can  be  distinguished 
in  a  vertical  section  of  the  water  of  the  ocean  : — 

(a)  A  first  zone,  highly  illuminated,  which  extends  from  the 
surface  to  about  30  metres  down. 

(ft)  The  shaded  zone,  from  about  30  metres  below  the  surface 
to  the  farthest  limits  to  which  light  penetrates  (some  500  metres 
deep). 

(c)  The  dark  zone,  which  commences  at  500  metres,  and  extends 
to  the  greatest  depth  known  to  be  inhabited,  i.e.  some  thousands 
of  metres  (in  the  Mediterranean  the  Puritan  dredged  to  a  depth 
of  some  1500  metres). 

It  agrees  with  this,  and  with  the  fact  that  light  is  an  indis- 
pensable condition  of  plant  life  (chlorophyll  function),  that  no 
vegetable  organisms  (algae)  have  so  far  been  dredged  at  a  lower 
level  than  the  shaded  zone,  i.e.  below  500  metres.  On  the  other 
hand,  numerous  animal  organisms  have  been  found,  and  described, 
below  this  level,  in  accordance  with  the  fact  that  light  is  not 
an  indispensable  vital  condition  to  animals.  It  is,  however, 
interesting  in  those  animals  which  live  entirely  in  the  dark,  to 
observe  the  morphological  changes  in  the  sense  organs  destined 
to  receive  luminous  stimuli  (eyes).  In  some  they  atrophy  com- 
pletely, as  in  terrestrial  creatures  living  in  caves;  in  others,  on 
the  contrary,  they  develop  enormously ;  while  in  order  to  furnish 
the  stimuli  required  to  make  them  perform  their  functions,  they 
develop  numerous  and  powerful  luminous  organs  in  different  parts 
of  the  body. 

Hensen  was  the  first  to  propose  the  collective  name  of  Plankton 
(ir\avKTo<s,  wandering),  which  is  now  universally  accepted,  to  indicate 
the  world  of  living  organisms  (fauna  and  flora)  in  mid-ocean ; 
while  the  name  of  Benthos  (ftcvOos,  bottom)  is  applied  to  the 
aquatic  organisms  that  live  at  the  bottom  of  the  sea. 

Lo  Bianco  (1903),  on  the  strength  of  the  facts  already  discussed, 
to  the  effect  that  light  is  the  factor  determining  the  varying  dis- 
tribution of  plankton,  proposed  to  term  the  biological  stratum 
which  corresponds  with  the  first  of  the  above  zones  phao-plankton, 


in  LIVING  MATTER  83 

the  organisms  living  in  the  second,  shaded  zone,  kneplio -plankton, 
and  those  living  in  the  third,  dark  zone,  scoto-plankton. 

Since,  beside  these,  there  are  many  organisms  which  live  in- 
differently on  the  surface  or  at  the  greatest  depths,  he  proposes  to 
collect  the  four  classes  together  under  the  collective  name  of  panic- 
plankton. 

This  is  not  the  place  in  which  to  enumerate  the  forms  and 
species  of  the  organisms  that  constitute,  respectively,  these  four 
great  classes  of  marine  life.  We  will  only  state  that  phao-plankton 
consists  principally  of  ova  that  find  in  this  zone  the  best  con- 
dition for  their  evolution,  and  of  the  larvae  or  young  forms  of 
organisms,  which  in  the  adult  state  live  either  at  the  bottom 
(benthonic  forms)  or  in  the  deeper  strata  of  the  sea.  Besides  the 
phao-plankton,  certain  species  of  Crustacea  (copepods)  are  abundant 
The  temperature  of  the  water  in  this  zone  oscillates  from  13°  C.  in 
winter  to  26°  C.  in  summer.  The  more  or  less  copious  contents  of 
the  phao-plankton  varies  with  the  seasons ;  it  is  particularly 
abundant  in  the  spring  because  reproduction  is  most  active  at  that 
season.  A  striking  characteristic  of  most  components  of  phao- 
plankton  is  their  minute  dimensions.  It  is  a  remarkable  fact  that 
many  pelagic  forms  are  larger  in  proportion  with  the  depths  at 
which  they  live. 

The  temperature  of  the  second  (shaded)  zone  varies  from  13°  to 
24°  C.  in  its  superficial  stratum,  and  by  a  couple  of  degrees  only  in  the 
deeper  parts, becoming  constant  (13°  C.  in  the  Mediterranean)  below 
that.  The  plankton  which  inhabits  this  region  (kneplio -planktoii) 
is  the  richest  of  all.  "  This  zone,"  writes  Lo  Bianco,  "  since  it  is 
sheltered  from  the  direct  rays  of  the  sun  and  movements  of  the 
waves,  is  the  habitat  most  favourable  to  pelagic  organisms ;  these 
physical  conditions  make  it  the  richest  and  most  varied  in  both 
plant  and  animal  forms." 

Many  varieties  of  scoto-plankton  are  brilliant  in  colour,  e.g. 
most  kinds  of  Crustacea  have  very  red  bodies. 

XIII.  After  discussing  the  general  conditions  and  external 
stimuli  of  cell  life,  we  ought,  in  another  chapter,  to  consider  the 
general  conditions  and  internal  stimuli,  i.e.  such  as  arise  within 
the  organism  itself,  and  which  govern  all  the  vital  phenomena  that 
appear  to  be  spontaneous  or  automatic — whether  these  originate 
in  predominatingly  katabolic  processes  (protoplasmic  movements, 
sensory  phenomena,  development  of  heat,  electricity,  and  light),  or 
are  due  to  predominatingly  anabolic  processes  (phenomena  of 
nutrition,  reproduction,  evolution).  Our  concrete  knowledge  of 
these  internal  conditions  and  stimuli  is,  however,  at  present  so 
fragmentary  that  a  few  paragraphs  will  contain  such  general 
notions  as  have  been  determined  in  relation  to  them. 

The  constitution  of  a  complete  elementary  organism,  capable, 
i.e.,  of  every  kind  of  essential  vital  activity,  requires  that  the 


84  PHYSIOLOGY  CHAP. 

protoplasm  shall  have  attained  a  certain  degree  of  organisation 
whether  chemico-physical  or  morphological,  so  as  not  to  be  homo- 
geneous in  any  individual  particle.  We  saw  in  Chapter  I. 
that  the  minimal  degree  of  organisation  necessary  to  constitute 
a  complete  organism  is  in  all  probability  represented  by  its 
differentiation  into  cytoplasm  and  nucleus.  A  homogeneous  bit 
of  living  matter  detached  from  an  elementary  organism,  either  of 
cytoplasm  or  of  nucleus,  is  incapable  of  prolonged  existence ;  on 
the  other  hand,  a  minute  particle  of  heterogeneous  protoplasm,  i.e. 
a  fragment  of  nucleus  and  cytoplasm  combined  (p.  13),  is  capable 
of  nutrition,  integration,  and  reproduction.  Vital  metabolism 
cannot  continue  without  the  natural  union  of  these  two  essential 
parts  of  the  cell,  showing  that  there  exist  between  them  reciprocal 
exchanges  of  matter  and  energy — the  universal  internal  condition 
of  cell  life. 

The  same  applies  to  complex  or  multicellular  organisms.  In 
the  lowest  grades  of  organisation,  it  is  possible  to  divide  a  multi- 
cellular  individual  into  one  or  more  segments  without  fear  of 
killing  it ;  each  segment  continues  to  live,  to  show  signs  of 
sensibility,  to  grow  and  regenerate  into  a  new  individual  like  that 
of  which  it  was  originally  a  part.  The  classical  example  of  this 
marvellous  phenomenon  was  given  for  the  first  time  on  animals, 
in  1774,  by  the  Genevese  naturalist  Trenibley,  with  fresh-water 
polyps.  The  interpretation  now  accepted  is  that  the  cells  of  which 
the  polyp  is  built  up  are  not  too  highly  differentiated  in  structure 
and  function  to  be  capable  of  mutual  substitution ;  each  cell,  i.e., 
represents  the  germ  of  the  entire  polyp,  and  can  therefore  recon- 
struct it. 

In  the  higher  grades  of  organisation,  on  the  contrary,  where 
there  is  a  more  or  less  advanced  differentiation,  both  morphological 
and  functional,  of  the  parts  that  constitute  the  organism  as  a 
whole,  it  is  no  longer  possible  to  multiply  the  individual  by 
sections,  because  the  life  of  each  part  is  conditioned  by  that  of  the 
others,  and  they  all  represent  integrating  factors  of  more  or  less 
importance  to  the  life  of  the  aggregate.  In  the  higher  vertebrates 
also  it  is  possible  to  amputate  a  limb  or  an  organ,  or  even  several 
limbs  or  organs,  without  necessarily  causing  death.  This  is  either 
because  the  function  of  the  lost  parts  can  be  replaced  by  others,  or 
because  there  is  not  between  the  missing  parts  and  those  which 
remain  a  reciprocal  exchange  of  matter  and  energy  sufficient  to 
make  them  indispensable  to  the  life  of  the  entire  aggregate,  in  the 
way  that  the  nucleus  is  necessary  to  the  life  of  the  cytoplasm 
and  the  cytoplasm  to  the  life  of  the  nucleus. 

We  know  nothing  positive  in  regard  to  the  conditions,  the 
internal  stumuli,  and  the  intimate  mechanism  of  the  phenomena 
of  the  nutrition  and  growth  of  protoplasm,  and  of  cellular  repro- 
duction or  neo- formation.  All  our  ideas  on  this  subject  are 


in  LIVING  MATTEK  85 

exclusively  morphological  and  are  treated  at  length  in  text-books 
of  histology,  to  which  the  reader  should  refer. 

Very  undetermined  also,  and  far  from  concrete,  is  our  know- 
ledge of  the  internal  conditions  and  stimuli  of  all  those  vital  acts 
of  which  protoplasm,  is  capable,  even  when  it  is  as  far  as  possible 
protected  from  every  external  agent  that  can  function  as  a 
stimulus,  by  deviating  from  the  general  external  conditions. 

Some  hold  that  the  stimulus  to  movement  and  other  auto- 
matic acts  arises  in  the  waste  products  that  develop  and  accumu- 
late in  the  cell,  in  consequence  of  its  metabolism.  In  this  case 
it  is  evident  that  both  automatic  excitations  and  reflexes  are 
the  effect  of  stimuli  extrinsic  to  the  protoplasm ;  but  in  the  former 
these  are  generated  by  the  activity  of  the  organism  itself,  in  the 
latter  they  come  from  without. 

The  intrinsic  fallacy  of  this  doctrine  is  easily  appreciated  when 
we  consider  that,  on  its  showing,  all  the  phenomena  of  excitation, 
paralysis,  or  of  fatigue  that  are  seen  in  the  different  forms  of  auto- 
intoxication must  be  regarded  as  automatic  phenomena,  because 
the  agents  by  which  they  are  determined  (e.g.  carbonic  acid, 
as  in  asphyxia  from  suffocation,  urinary  products,  as  in  uraemia, 
muscular  toxins,  as  in  fatigue  or  exhaustion  consequent  on  exces- 
sive and  prolonged  muscular  exertion)  all  originate  in  the  meta- 
bolic activity  of  the  different  tissues  of  the  body. 

The  true  concept  of  automaticity  is  very  different :  either  we 
must  demonstrate  that  there  are  no  automatic  phenomena,  properly 
speaking,  or  we  must  hold  that  the  stimulus,  or,  more  generically, 
the  determining  cause  of  the  phenomena,  is  intrinsic  to  the 
elementary  organism  which  exhibits  them,  and  consists  in  an  oscil- 
lation (rhythmical  or  irregular)  of  its  metabolism  or  its  excitability, 
by  which  it  finds  within  itself  the  conditions  for  the  development 
of  the  energy  it  has  stored  up  (Luciani,  1873).  The  chemical  and 
molecular  transmutations  of  protoplasmic  metabolism  are  usually 
conceived  as  something  continuous  and  monotonous,  which  can 
only  be  changed  or  modified  by  external  influences ;  but  nothing 
forbids  us  to  imagine  a  more  vital  process,  which  without  invoking 
external  factors  may  become  disturbed  of  itself,  or  in  consequence 
of  the  particular  structure  of  the  protoplasm,  or  the  facility  with 
which  the  particles  of  which  it  is  composed  are  able  to  change  their 
relations. 

XIV.  Various  hypotheses  and  theories  have  been  put  forward 
as  to  the  nature  of  the  intimate  processes  that  go  on  in  living 
matter,  and  by  which  the  several  vital  phenomena,  thus  briefly 
summarised,  are  determined.  The  starting-point  and  fundamental 
concept  from  which  these  different  speculations  have  for  the  most 
part  been  evolved  is  invariably  the  same,  starting  from  the  oft- 
accentuated  hypothesis  that  chemical  energy  is  to  be  regarded  as 
the  sole  and  ultimate  cause  of  all  the  manifestations  exhibited  by 


86  PHYSIOLOGY  CHAP. 

living  organisms — which  chemical  energy,  introduced  into  the 
animal  body  in  the  potential  form  by  the  different  complex  food- 
stuffs, becomes  free  or  kinetic,  owing  to  the  activity  of  the  living 
protoplasm. 

From  this  it  may  be  deduced  that  the  living  organism  is 
distinguished  from  the  dead  in  virtue  of  the  incessant  metabolism, 
or  exchange  of  materials,  which  is  taking  place,  even  when  it  is 
apparently  in  the  state  of  most  complete  repose.  These  material 
exchanges  are,  of  course,  associated  with  exchanges  of  energy. 

Pfliiger,  in  his  classical  essay  on  Physiological  Combustion  in 
Living  Organisms  (Pfliiger s  Arch.  x.  1875),  recognised  on  the 
strength  of  many  different  experimental  data  that  the  essential 
characteristic  of  living  matter  consists  in  its  being  highly  un- 
stable, splitting  up  and  regenerating  itself  incessantly. 

"  The  fact,"  he  writes,  "  which  every  biologist  encounters  on  all 
sides,  is  the  amazing  instability  (Zersetzbarkeif)  of  almost  all  living 
matter.  .  .  .  This  instability  is  the  cause  of  excitability.  Does 
not  the  infinitesimal  vital  force  of  a  ray  of  light  evoke  the  most 
potent  effects  in  brain  and  retina  ?  I  think  no  one  will  deny  that 
living  matter  is  not  merely  highly  unstable  (zersetzbqf),  but  also 
that  it  is  continually  breaking  up  (zersetzend)"  The  ultimate 
cause  of  these  chemical  transmutations,  and  of  the  continuous 
atomic  and  molecular  transformations  of  living  matter,  lies  in  the 
intra-molecular  heat  which  comes  into  play  in  virtue  of  the  specific 
nature  of  living  matter. 

In  summing  up  his  theory  Pfliiger  concludes :  "  The  vital 
process  is  the  intra-molecular  heat  of  the  highly  unstable 
(zersetzbarer)  molecules  of  protein  present  in  the  cell -substance, 
which  split  up  (zersetzender)  by  dissociation — with  formation  of 
carbonic  acid,  water,  and  starch  compounds — and  which,  on  the 
other  hand,  are  perpetually  regenerated,  and  also  increase  by 
polymerisation." 

We  saw  in  the  last  chapter  that  Metabolism  may  be  regarded 
as  the  result  of  two  opposite  antagonistic  processes:  the  ana- 
bolic, synthetic,  restorative  process,  and  the  katabolic,  analytic, 
disintegrative  process.  E.  Hering  (1888)  gave  to  the  former  the 
name  of  Assimilation,  to  the  latter  that  of  Dissimilation,  and  laid 
down  certain  important  considerations  in  regard  to  the  theory  of 
the  intimate  processes  of  living  matter. 

He  starts  from  the  indisputable  fact  that  living  matter  at  any 
given  moment  is  the  seat  of  two  opposite  processes  which  arise  and 
proceed  simultaneously,  even  when  no  external  stimulus  is  acting 
on  the  living  matter.  He  gave  the  name  of  autonomous  assimila- 
tion (A)  and  autonomous  dissimilation  (D)  to  those  processes 
which  take  place  in  living  matter,  when  no  external  stimulus 
intervenes.  If  these  two  opposite  processes  are  equal,  so  that 
neither  the  one  nor  the  other  predominates,  then  the  substance 


in  LIVING  MATTEE  87 

alters  neither  quantitatively  nor  qualitatively ;  we  have  what 
Hering  terms  autonomous  equilibrium. 

But,  as  we  have  seen,  external  stimuli  are  continually  acting 
upon  living  matter  and  modifying  the  state  of  its  metabolism. 
Hering  distinguishes  two  kinds  of  stimuli,  which  differ  essentially 
inter  se,  inasmuch  as  the  one  kind  excite  the  dissimilatory  phase 
(dissimilatory  stimuli) — and  these  are  more  usually  noticed — 
while  the  other  kind  act  by  exciting  or  augmenting  the  phase  of 
assimilation  (assimilatory  stimuli). 

Assuming,  then,  the  action  of  a  dissimilatory  stimulus, 
dissimilation  will  be  increased,  and  is  termed  by  Hering  allono- 
mous  dissimilation :  the  living  substance  changes  in  its  quality 
and  quantity,  and  has  a  lower  energy  value  (is  "below  par"). 
Hering  assumes  that  in  proportion  as  the  living  matter,  under 
the  influence  of  this  stimulus,  is  excited  to  increased  dissimila- 
tion, its  inherent  tendency  to  the  dissimilatory  phase  diminishes 
while  its  inherent  tendency  to  the  assimilatory  phase  increases. 
Owing  to  this  property,  which  he  terms  the  internal  automatic 
regulation  of  living  matter,  at  the  close  of  the  dissimilatory 
stimulus  the  opposite  process  of  assimilation  sets  in  more 
vigorously  than  usual,  so  that  after  a  certain  time  the  living 
matter  regains  the  mean  energy  value  of  equilibrium  (i.e.  is  "  at 
par  " )  towards  which  it  strives — the  more  incessantly,  and  with 
so  much  the  greater  energy,  the  farther  it  is  removed  from  the 
said  equilibrium  in  the  one  direction  or  the  other,  by  the  action  of 
external  stimuli. 

It  may,  however,  happen  that  the  dissimilatory  stimulus  does 
not  cease,  but  persists  for  an  indefinite  time ;  then  in  consequence 
of  the  diminished  dissimilatory  activity,  and  the  simultaneous 
increase  in  autonomous  assimilation,  a  new  state  of  equilibrium  is 
finally  arrived  at,  which  Hering  terms  allonomous  equilibrium, 
and  which  prevails  so  long  as  the  dissimilatory  stimulus  is  acting. 
The  living  matter  has  adapted  itself  to  the  prolonged  action  of  the 
stimulus. 

The  same  reasoning  holds  for  the  action  of  the  assimilatory 
stimuli,  which  provoke  an  increase  in  the  assimilatory  process. 

Verworn,  in  his  General  Physiology  (1895),  has  developed 
Hering's  doctrine,  while  he  takes  Pfiiiger's  theory  also  into 
consideration. 

"  Pfliiger's  assumption  of  living  protein,  which  distinguishes 
living  cell-substances  from  dead,  and  in  the  loose  constitution  of 
which  lies  the  essence  of  life,  is  necessitated.  But  this  substance 
must  be  of  essentially  different  composition  from  dead  protein, 
although,  as  follows  from  the  character  of  its  decomposition- 
products,  certain  characteristic  atomic  groups  of  the  proteins 
are  contained  in  it.  The  great  lability  that  distinguishes  it 
from  other  proteins,  can  be  conditioned  only  by  an  essentially 


88  PHYSIOLOGY  CHAP. 

different  constitution.  In  order  to  distinguish  this  body,  there- 
fore, from  dead  protein,  and  to  indicate  its  high  significance  in 
the  occurrence  of  vital  phenomena,  it  appears  fitting  to  replace 
the  term  '  living  protein  '  with  that  of  biogen.  The  expressions 
'plasma  molecule/  'plasson  molecule/  'plastidule/  etc.,  whiah 
Elsberg  and  Haeckel  have  employed,  and  the  conceptions  of 
which  are  comprised  approximately  in  the  expression  'biogen 
molecule/  are  less  fitting  in  so  far  as  they  easily  give  the 
impression  that  protoplasm  is  a  chemically  unitary  body,  which 
consists  of  wholly  similar  molecules;  such  a  view  must  be  ex- 
pressly rejected.  Protoplasm  is  a  morphological,  not  a  chemical 
conception." 

Verworn  gives  the  name  of  Biotonus  to  the  ratio  between  the 
assimilatory  and  dissimilatory  processes,  which  Hering,  as  we  have 
seen,  regards  as  the  theoretical  foundation  of  the  processes  that  go 
on  in  living  matter. 

"  If  we  consider,"  he  goes  on,  "  the  quantitative  relation  of 
assimilation  to  dissimilation  in  a  considerable  mass  of  living 
substance,  such,  for  example,  as  is  contained  in  a  cell,  we  find  it 
very  variable,  and  even  without  the  influence  of  stimuli  it  changes 
within  wide  limits.  This  relation  of  the  two  processes  in  the  unit 

of  time,  which  can  be  expressed   by  the  fraction  ^  and  will  be 

termed,  in  brief,  biotonus,  is  of  fundamental  importance  for  the 
various  phenomena  of  life.  The  variations  in  the  value  of  the 
fraction  effect  all  changes  in  the  vital  manifestations  of  every 
organism. 

"  The  fraction  ^-  is  merely  a  general  form  of  the  expression 

of  biotonus.  In  reality,  assimilation  and  dissimilation  are  not 
simple  processes  ;  on  the  contrary,  the  events  that  lead  to  the 
construction  of  the  biogen  molecule,  and  the  formation  of  the 
decomposition-products,  are  very  complex  and  consist  of  processes 
closely  interwoven.  Hence  if  we  would  express  biotonus  in  a 
specialised  way,  we  must  give  the  fraction  the  form 


in  which  a,  av  a.2,  a3,  etc.,  and  d,  dv  d2,  ds,  etc.,  represent  the 
partial  processes  that  combine  to  form  the  whole." 

With  our  present  limited  knowledge  of  the  more  special 
transformations  that  take  place  in  living  substance,  it  is  impossible 
approximately  to  gauge  the  significance  of  the  individual  com- 
ponents of  the  .biotonous  quotient.  Verworn,  therefore,  refers 

only  to  considerations  arising  from  the  general  formula  g. 

Where  assimilation  and  dissimilation  are  equal  in  the  unit  of 


in  LIVING  MATTEE  89 

time,  the  fraction  g  =  1,  Bering's  metabolic  equilibrium.     In  this 

state,  the  sum  of  the  excreted  substances  of  every  kind  is  equal  to 
the  sum  of  the  ingested  substances. 

"  If  the  individual  members  of  series  A  increase  in  a  constant 
relation  to  one  another,  while  the  members  of  series  D  remain 
equal  or  decrease,  so  that  in  the  unit  of  time  the  sum  of  the 
members  of  A  is  greater  than  that  of  the  members  of  D,  then  the 

metabolic  quotient  ^>1- 

"  This  case  is  realised  in  growth,  where  the  formation  of  living 
substance  surpasses  its  destruction. 

"  If,  vice  versa,  the  members  of  series  D  grow  proportionately  to 
one  another,  while  those  of  series  A  remain  unchanged,  or  become 

smaller,  biotonus  *f>1-      This  condition  is  the  basis  of  atrophy, 

and  leads  finally  to  death." 

In  a  later  work  (1903)  Verworn  developed  this  theory  more 
fully,  giving  it  the  name  of  Biogen  hypothesis  and  enumerating 
the  various  indirect  arguments,  of  early  or  recent  date,  which  tell 
in  its  favour,  and  show  how  by  its  application  we  may  arrive  at  a 
unitary  explanation  of  the  action  of  the  several  stimuli  upon 
living  matter. 

"In  my  opinion"  (he  concludes)  "the  principal  value  of  the 
biogen  hypothesis  lies  in  the  fact  that  it  enables  us  to  gather  up 
all  the  vital  phenomena  under  .a  single,  very  definite  and  simple 
point  of  view,  without  contradicting  any  of  the  facts  hitherto  noted. 
This  hypothesis  provides  us  with  a  clear  idea  of  the  phenomena 
fundamental  to  the  whole  of  life,  and  is  thus  of  singular  utility 
in  facilitating  the  interpretation  of  many  complex  and  controverted 
problems." 

"  Still "  (he  adds)  "  it  must  once  more  be  pointed  out  that  this 
is  merely  a  working  hypothesis,  and  that  it  would  be  quite 
fallacious  to  attribute  to  it  any  other  value.  Whether  it  be  a 
faithful  representation  of  the  real  facts,  or  whether  it  be  in- 
adequate, matters  little  ;  as  a  working  hypothesis  it  keeps  its 
value  so  long  as  it  is  useful  and  fecund  in  the  progress  of  science. 
The  history  of  science  is  richer  in  fallacies  than  in  truth ;  but  in 
the  development  of  the  human  mind  a  fertile  error  is  of  infinitely 
greater  value  than  a  sterile  fact." 

BIBLIOGRAPHY 

In  addition  to  the  general  treatises  on  animal  and  plant  physiology  cited  above 

see  : — 

PFLUGER.     Pfliigers  Arch.  x.  1875. 

Cl.  BERNARD.  Lecons  sur  les  phenomenes  de  la  vie  commune  aux  animaux  et  aux 
vegetaux.  Paris,  1878-79. 

E.  HERING.  Vorgange  d.  lebender  Materie,  "  Lotos,  "ix.  1888.  (English  transla- 
tion, Theory  of  the  Functions  of  Living  Matter,  by  F.  A.  VVelby.  Brain, 
xx.  1897.) 


90  PHYSIOLOGY  CHAP,  in 

J.  ROSENTHAL.     Lehvbuch  d.  allg.  Physiologie.     Leipzig,  1901. 

S.  Lo  BIANCO.     Mitteilungen  aus  d.  zoolog.  Station  zu  Neapel,  xvi.  1903. 

M.  VERWORN.     Allgemeine    Physiologie.      Jena.      G.    Fischer.      4th   ed.,    1903. 

(English  translation  by  Dr.  F.  S.  Lee.     Macmillan.) 
M.  VERWORN.     Die  Biogenhypothese.     Jena.     Fischer,  1903. 
J.    LOEB.     Studies  in  General  Physiology.     Chicago,  1905. 

Recent  English  Literature  : — 
E.   W.    TOWLE.      A  Study  in  the  Heliotropism  of  Cypridopsis.      Amer.  Journ. 

of  Physiol.,  1900,  iii.  345. 
J.    LOEB.      On  lon-proteid  Compounds  and  their  role  in  the   Mechanics  of  Life 

Phenomena.     Part  I.     Amer.  Journ.  of  Physiol.,  1900,  iii.  327. 
R.  M.  YEUKES.     Reaction  of  Entoniostraca  to  Stimulation  by  Light.     1.     Amer. 

Journ.  of  Physiol.,  1900,  iii.  157. 
R.  M.  YERKES.     Reaction  of  Entomostraca  to  Stimulation  by  Light.     II.     Amer. 

Journ.  of  Physiol.,  1901,  iv.  405. 

R.  PEARL.     Studies  on  Electrotaxis.     I.  Amer.  Journ.  of  Physiol.,  1901,  iv.  96. 
R.  PEARL.     Studies  on  the  Effects  of  Electricity  on  Organisms.    II.    Amer.  Journ. 

of  Physiol.,  1901,  v.  301. 
E.  B.  HOLT  and  F.  S.  LEE.     The  Theory  of  Phototactic  Response.     Amer.  Journ. 

of  Physiol.,  1901,  iv.  460. 
H.  H.  DALE.     Galvanotaxis  and  Chemotaxis  of  Ciliate  Infusoria.     Part  I.     Journ. 

of  Physiol.,  1900-1,  xxvi.  291. 
"NV.    M.    FLETCHER.     The   Relation   of  Oxygen   to   the  Survival   Metabolism   of 

Muscle.     Journ.  of  Physiol.,  1902,  xxviii.  474. 
R.   S.    LILLIE.     On  Differences  in  the  Direction  of  the  Electrical  Convection  of 

certain  Free  Cells  and  Nuclei.     Amer.  Journ.  of  Physiol.,  1903, 'viii.  273. 
G.  P.  ADAMS.      On  the  Negative  and  Positive  Phototropism  of  the  Earthworm 

Allolobophora  foetida,    as    determined    by    Light    of    Different    Intensities. 

Amer.  Journ.  of  Physiol.,  1903,  ix.  26. 
A.   Moo  HE.     Some  Facts  concerning  Geotropic  Gatherings  of  Paramoecia.     Amer. 

Journ.  of  Physiol.,  1903,  ix.  238. 
E.  TORELLE.     The  Response  of  the  Frog  to  the  Light.     Amer.  Journ.  of  Physiol., 

1903,  ix.  466. 
E.   P.    LYON.     On  Rheotropism.     I.   Rheotropism  in   Fishes.      Amer.  Journ.   of 

Physiol.,  1904,  xii.  149. 
E.  P.  LYON.     On  Rheotropism.     Part  II.     Amer.  Journ.  of  Physiol.,  1909,  xxiv. 

244. 
G.  SMITH.     The  Effect  of  Pigment-Migration  on  the  Phototropism  of  Gammarus 

annulatus,  S.  I.  Smith.     Amer.  Journ.  of  Physiol.,  1905,  xiii.  205. 
E.  P.  LYON.     On  the  Theory  of  Geotropism  in  Paramoecium.     Amer.  Journ.  of 

Physiol.,  1905,  xiv.  421. 
E.  P.  LYON.     An  Outline  of  a  Theory  of  the  Genesis  of  Protoplasmic  Motion  and 

Excitation.     Trans.  Roy.  Soc.  of  South  Australia,  1905,  xxix.  7. 
T.  B.  ROBERTSON.     Investigations  on  the  Reactions  of  Infusoria  to  Chemical  and 

Osmotic  Stimuli.     Journ.  of  Biolog.  Chem.,  1905-6,  i.  185. 
O.    P.  TERRY.      Galvanotropism  of  rolvox.      Amer.  Journ.  of  Physiol.,  1905-6, 

xv.  235. 
J.  "VV.  BANCROFT.     On  the  Influence  of  the  Relative  Concentration  of  Calcium  Ions 

on  the  Reversal  of  the  Polar  Effects  of  the  Galvanic  Current  in  Paramoecium. 

Journ.  of  Physiol.,  1906,  xxxiv.  444. 
P.  B.  HADLEY.     The  Relation  of  Optical  Stimuli  to  Rheotaxis  in  the  American 

Lobster  Homarus  americanus.     Amer.  Journ.  of  Physiol.,  1906-7,  xvii.  326. 
P.    B.    HADLEY.      Galvanotaxis   in   Larvae   of   the   American  Lobster  Homarus 

americanus.     Amer.  Journ.  of  Physiol.,  1907,  xix.  39. 
J.   R.  MILLER.     Galvanotropismus  in  the  Crayfish.     Journ.  of  Physiol.,  1906-7, 

xxxv.  215. 


CHAPTER    IV 

THE    BLOOD  :    FORMED    CONSTITUENTS 

SUMMARY. — 1.  Arrangement  of  human  physiology,  and  classification  of 
functions.  2.  Importance  of  the  blood  as  centre  of  the  vegetative  system 
and  agent  of  general  metabolism.  3.  Historical  development  of  haematology. 
4.  General  physico-chemical  characters  of  the  blood.  5.  Estimation  of  total 
quantity.  6.  Physical  and  morphological  characters  of  erythrocytes,  and 
estimation  of  their  relative  quantity.  7.  Chemical  composition.  Properties  of 
haemoglobin  and  its  derivatives.  8.  Character,  composition,  and  physiological 
properties  of  leucocytes.  9.  Blood  platelets,  and  elementary  granulation  of  the 
blood.  Bibliography. 

JUST  as  no  absolute  difference  can  be  admitted  between  the  vital 
activities  of  plants  and  animals,  so  no  absolute  difference  can  be 
recognised  between  the  functions  of  the  individual  living  cells, 
tissues,  organs,  and  systems  of  which  the  higher  organisms, 
including  man,  consist.  It  is  nevertheless  to  be  observed  that  in 
all  complex  organisms,  whether  animals  or  plants,  there  is  pari 
passu  with  the  morphological  differentiation  of  the  primitive  cell, 
which  occurs  during  ontogenic  development,  a  functional  differ- 
entiation, resulting  in  a  division  of  labour,  i.e.  in  the  greater 
or  less  specialisation  of  the  capacities  or  functions  of  the  different 
parts.  As  in  the  great  industries  an  ever-increasing  development 
and  perfection  of  industrial  products  is  obtained  with  the  pro- 
gressive division  of  the  work  assigned  to  the  various  groups  of 
workmen,  so  the  increasing  perfection  observed  in  the  scale  of 
living  beings  is  essentially  the  result  of  progressive  morphological 
differentiation  and  functional  specialisation  in  the  cells  of  which 
the  organism  is  composed  (Milne  Edwards,  1827).  It  is  evident 
that  the  arrangement  of  the  special  physiology  of  man,  and 
the  rational  classification  of  his  functions,  must  rest  upon  this 
specialisation  of  the  different  organs  and  systems  in  the  higher 
animals. 

I.  At  the  commencement  of  the  nineteenth  century  Xavier 
Bichat,  in  his  inspired  book  Sur  la  vie  et  la  mort,  made  a  sharp 
distinction  between  two  orders  of  functions  in  the  higher 
organisms,  which  he  designated  as  the  functiqns  of  organic  (or 
vegetative)  life  and  the  functions  of  animal  life  respectively. 

91 


92  PHYSIOLOGY  CHAP. 

By  means  of  the  former,  says  Bichat  in  effect,  these  organisms  are 
constantly  transforming  into  their  own  substance  the  materials 
which  they  receive  from  outside,  while  they  continually  eliminate 
the  useless  products  of  consumption  ;  by  means  of  the  latter,  they 
feel  and  perceive  the  external  world,  express  their  sensations, 
perform  voluntary  movements  under  the  influence  of  these,  and 
are  able  to  express  their  desires  and  fears,  their  pains  and 
pleasures. 

Although  modern  science  has  established  the  unitary  con- 
ception of  life,  and  has  refuted  the  supposed  antagonism  between 
the  functions  of  plants  and  of  animals,  Bichat's  general  distinction 
holds  good  as  the  basis  of  a  rational  classification.  It  is  a  fact 
that  the  cardinal  function  of  plants,  taken  as  a  whole,  is  the 
synthetic  building-up  of  organic  matter,  while  that  of  animals  is 
its  disintegration. 

On  the  other  hand,  it  is  undeniable  that  the  higher  animals 
possess  a  system  of  organs  and  apparatus  which  essentially  serve 
the  internal  life  of  the  body,  by  preparing  and  constantly  re- 
newing the  pabulum  common  to  all  the  living  elements  of  which 
it  consists :  while  there  is  a  second  system  which  especially  serves 
the  external  life,  by  developing  the  potential  energy  of  the  living 
matter.  The  first  system  recalls  the  predominance  of  anabolism 
in  plants,  as  compared  with  animals  ;  the  second  the  predominance 
of  katabolism  in  animals,  as  compared  with  plants. 

Yet,  if  we  attempt  to  determine  exactly  which  organs  and 
apparatus  compose  the  vegetative  system,  in  distinction  to  those 
of  which  the  animal  system  consists,  we  encounter  difficulties. 
The  embryological  criterion,  so  often  invoked  in  this  connection, 
i.e.  the  derivation  of  the  different  parts  from  one  or  other  of  the 
three  germinal  layers,  leads  to  no  satisfactory  result,  since  it  is 
now  well  established  that  tissues  and  organs  are  developed  from  the 
external,  and  yet  more  from  the  middle,  layer,  which  obviously 
belong  some  to  one  system  and  some  to  the  other.  Clearly  these 
two  systems  do  not  represent  two  distinct  and  superposed  organisms, 
but  rather  two  that  are  intimately  connected  and  interdependent, 
to  be  distinguished  only  by  artificial  means,  contingent  to  a  certain 
extent  on  individual  judgment  and  appreciation. 

It  is  the  obvious  function  of  the  vegetative  system,  as  a  whole, 
to  keep  constant  the  quantity  and  quality  of  the  mass  of  blood, 
from  which  is  formed  the  lymph  or  plasma  constituting  the 
common  internal  medium  indispensable  to  the  life  of  each  vital 
element.  This  system  consists  necessarily  of  the  blood,  of  the 
cardio- vascular  apparatus  by  means  of  which  it  circulates,  and  of 
the  whole  of  the  glandular  organs  and  apparatus  designed  for  its 
constant  renewal,  elaboration,  and  cleansing. 

On  the  other  hand,  the  function  of  the  animal  system  is  to 
bring  the  animal  through  its  sense  organs  into  relation  with  the 


iv  THE  BLOOD:   FOKMED  CONSTITUENTS  93 

external  world,  and  to  modify  these  relations  in  various  ways  by 
means  of  the  organs  of  motion.  It  consists  accordingly  of  the 
central  and  peripheral  nervous  system,  i.e.  the  sensory  and 
conducting  organs,  and  of  the  muscular  and  skeletal  system,  i.e. 
the  active  and  passive  apparatus  of  movement. 

The  blood  is  the  centre  and  objective  of  all  the  functions  of 
the  vegetative  system ;  the  brain  is  the  central  seat  and  focus  of 
the  functions  of  the  animal  system. 

A  third  order  of  physiological  processes  must  further  be  dis- 
tinguished from  the  special  functions  of  the  vegetative  and  animal 
systems,  in  which  both  these  and,  in  a  certain  sense,  the  entire 
organism  participate.  These  are  the  physiological  phenomena 
of  general  metabolism  and  the  regulation  of  the  balance  of  output 
and  intake ;  thermogenesis  and  the  regulation  of  the  heat  balance  \. 
sexual  and  reproductive  functions ;  the  physiology  of  the  embryo, 
and  of  the  different  stages  of  uterine  life. 

II.  As  centre  of  the  vegetative  system,  the  blood  contains  all 
the    histogenic    substances   destined  to   nourish   and   renew  the 
tissues,  and  all  the  histolytic  products  of  consumption,  useless  or 
noxious  residues,  to  be  eliminated.     The  first,  which  filter  through 
the  living  walls  of  the  capillaries,  pass  in  the  form  of  lymph  into 
the  interstitial  plasma-spaces  of  the  tissues  for  which  they  provide 
aliment;  the  second,  secreted  by  the  tissue  cells,  pass  into  the 
blood  by  way  of  the  lymph  vessels,  and  are  thence  eliminated  by 
the  kidneys,  lungs,  skin,  and  liver. 

From  the  histological  standpoint  the'  blood  may  be  regarded 
as  a  tissue.  It  contains  a  number  of  formed  elements,  represented 
by  the  corpuscles,  and  an  intercellular  substance,  the  plasma, 
which  is  essentially  a  product  elaborated  and  secreted  by  all  the 
cells  which  take  part  in  haeniatopoiesis  and  haematolysis.  The 
blood  is  distinguished  from  the  other  tissues  by  the  fact  that  it 
is  fluid  and  that  it  circulates,  and  is  therefore  capable  of  exerting 
its  action  on  all  the  fixed  tissues,  bringing  them  into  relation 
and  binding  them  together.  It  thus  functions  as  the  centre  of 
the  vegetative  system,  and  is  the  agent  of  metabolism,  i.e.  of  the 
material  exchanges  of  the  whole  body. 

III.  To  compress  within  a  few  lines  the  historical  development 
of  our  physiological  knowledge  of  the  blood  would  be  a  work  of 
difficulty.     In   this  field  there  is  no  one  great   discovery  to  be 
recorded,  only  the  gradual  acquisition  of   separate  facts  due  to 
the  labours   of  a  vast  number  of  observers.     We   shall  confine 
ourselves  to  enumerating  a  few  of  the  principal  dates  and  names 
as  landmarks. 

The  Italian  Malpighi  (1661)  was  the  first  who  saw  the  red 
corpuscles,  while  the  Dutch  Leeuwenhoek  (1673)  first  described 
them  accurately.  In  England  Hewson  (1770)  also  observed  the 
leucocytes,  found  that  many  salts  delayed  or  inhibited  coagulation,. 


94  PHYSIOLOGY  CHAP. 

and  foresaw  many  of  the  theories  that  are  now  generally  accepted. 
A  few  years  later  (1794)  J.  Hunter  published  an  extensive  work 
on  the  blood,  which  contained  not  a  few  new  observations  and 
ingenious  experiments.  Just  as  the  history  of  the  physics  and 
morphology  of  the  blood  begins  only  in  the  seventeenth  century 
with  the  discovery  of  the  microscope,  so  the  history  of  its 
chemistry  only  assumes  notable  proportions  at  the  commencement 
of  the  nineteenth  century,  after  Priestley  (1775)  and  Lavoisier 
(1784)  had  laid  the  h'rst  methodical  principles  of  modern 
chemistry.  As  the  precursors  of  our  present  science  of  haema- 
tology,  we  may  name  Berzelius  (1808),  Prevost  and  Dumas  (1821), 
Chevreul  (1824),  Nasse  (1842),  Simon  (1842),  Mulder  (1849), 
Lehmann  (1850)  and  many  others. 

IV.  If  we  consider  the  most  striking  characters  of  the  blood, 
it  is  found  to  be  a  red  fluid  (arterial  blood,  scarlet ;  venous  blood, 
dichroic,  i.e.  dark  red  in  reflected,  greenish  in  refracted,  light), 
somewhat  viscous,  opaque  even  in  thin  layers,  faintly  salt  and 
sweetish  in  taste,  with  a  characteristic  odour.  It  is  a  little 
heavier  than  water :  the  specific  gravity  of  a  man's  blood  varies 
between  1-057  and  1'066,  that  of  a  woman  from  1-053  to  1-061. 
The  reaction  of  the  blood  circulating  in  the  vessels  is  alkaline  in 
the  normal  state ;  extracted  from  the  vessels,  it  becomes  neutral 
and  then  slightly  acid.  It  must,  however,  be  noted  that  in  all  blood 
reactions,  and,  generally  speaking,  in  all  the  fluids  of  the  body,  we 
have  to  distinguish  between  the  actual  or  true  reaction  and  the 
potential  reaction. 

Eecent  researches  in  physical  chemistry  have  brought  out  the 
fundamental  fact  that  the  degree  of  acidity  or  alkalinity  of  a 
solution  is  determined  by  its  content  of  H  +  ions  and  OH  -  ions 
respectively.  Since  the  actual  reaction  of  a  liquid  is  that  which 
represents  its  content  of  free  H  +  or  OH  -  ions,  it  is  necessary 
in  determining  it  to  make  use  of  means  which  do  not  alter  the 
numbers  of  these  ions.  The  potential  reaction  is  that  which 
represents  the  degree  of  acidity  or  alkalinity  of  a  liquid  when 
the  electrolytes  which  it  contains  are  all  fully  dissociated  into 
their  ions. 

The  determination  of  these  two  kinds  of  reaction  leads  in  the 
case  of  the  blood  to  very  different  results.  While  according  to 
the  potential  reaction  the  alkalinity  of  the  blood  corresponds 
to  a  soda  solution  of  0'2  -  0'4  per  cent,  according  to  the  actual 

1-3 

or  true  reaction  it  would  be  that  of  IQQQOOOO-^  °^  s°da,  which  is 
practically  neutral  (Farkas). 

The  Pycnometric  Method  is  certainly  the  most  exact  for  determining  the 
specific  gravity  of  blood  in  animals,  and  also  in  man  when  there  is  a  sufficient 
quantity  of  blood  to  work  with.  A  glass  pycnometer  is  used,  which  carries  a 
thermometer  in  its  stopper  so  that  the  temperature  at  which  the  experiment 


IV 


THE  BLOOD:   FORMED  CONSTITUENTS 


95 


Fu;.  24.— Pycnometer  for  de- 
termining the  specific 
gravity  of  blood. 


is  carried  on  can  be  recorded  (Fig.  24).  After  carefully  cleaning  and  drying 
the  pycnometer,  it  is  weighed,  first  empty,  then  when  filled  with  distilled 
water.  It  is  then  washed  out  with  alcohol  and  ether,  dried  again,  and 
weighed  once  more  when  filled  with  the  blood  to  be  examined.  The  weighing 
must  be  accurate  to  iV  mgrm.  The  weight  of  distilled  water  at  15°  C.  being 
equal  to  1,  it  is  easy  to  calculate  that  of  blood  at  the 
same  temperature.  The  areometric,  method,  also  used 
in  physiology,  is  more  rapid,  but  is  less  exact  than 
the  pycnometric,  because  it  determines  the  specific 
gravity  of  the  plasma  rather  than  that  of  the  blood 
in  toto.  When  only  small  quantities  of  blood  are 
available,  as  in  clinical  researches,  the  capillary 
pycnometer  of  Schmalz  is  employed,  which  consists 
of  a  capillary  tube  some  12  cm.  long  by  1^  mm.  wide, 
in  which  distilled  water  and  1  tlood  are  aspirated  and 
weighed  in  succession.  The  weighing  and  calculat- 
ing are  carried  out  as  in  the  first  case. 

Besides  these  direct  methods  of  ascertaining 
specific  gravity  for  small  quantities  of  blood,  there 
are  other  indirect  ways  which  are  all  based  on  the 
principle  of  obtaining  from  a  more  dense  and  a  less 
dense  substance  a  mixture  of  the  same  density  as  the 
drop  of  blood  to  be  examined.  This  is  ascertained 
when,  on  introducing  the  drop  of  blood  into  the 
mixture  with  a  pipette,  the  drop  neither  sinks  nor 
rises  to  the  surface.  The  density  of  the  mixture  is 
then  determined  with  the  areometer,  and  will  be  that 
of  the  blood.  The  various  indirect  methods  differ  among  themselves  according 
to  the  quality  of  the  substances  used  for  the  mixture.  Fano  employs  a 
solution  of  gum,  Roy  a  solution  of  glycerin.  It  should  be  noted  that  these 
indirect  methods  rather  determine  the  specific  gravity  of  the  corpuscles  than 
that  of  the  blood  in  toto. 

When  care  is  taken  to  employ  liquids  in  which  the  components  of  blood 
are  the  least  soluble  (for  example  chloroform  and  benzol,  Hammerschlag's 
method),  these  methods  can  be  used  with  approximate  accuracy,  and  they 
may  also  be  employed  for  the  separate  determination  of  the  specific  gravity 
of  serum  (1028)  and  of  the  red  corpuscles  (1088). 

The  following  methods  are  used  in  determining  the  chemical  reaction  of 
the  blood  :— 

1.  Kuhne's  Method — The  drops  of  blood  to  be  examined  are  placed  in  a 
small  dialyser,  made  of  moist  parchment,  shaped  by  pressure  over  a  hemi- 
spherical mould.     The  drops  of  blood  are  introduced  into  the  resulting  hollow, 
and  the  whole  placed  in  a  watch-glass  containing  distilled  water,  to  dialyse. 
After  a  certain  time  the  reaction  of  this  water  is  tested  with  litmus-paper. 

2.  Liebreich's  Method. — A  drop  of  the  blood  to  be  examined  is  put  on  a 
slab  of  chalk  or  plaster,  previously  saturated  with  a  neutral  litmus  solution. 
After  a  given  time  the  slab  is  washed  with  a  vigorous  spray  of  distilled  water, 
and  the  spot  where  the  blood-drop  lay  is  found  to  be  more  or  less  blue  in 
correspondence  with  its  alkalinity. 

3.  Zuntz'  Method. — Glazed  strips  of  neutral  litmus-paper  are  used,  which 
are  saturated  with  a  solution  of  sodium  chloride  or  sodium  sulphate.     After 
bringing  these  into  contact  with  the  blood  to  be  examined,  they  are  washed 
rapidly  with  a  fine  spray  of  distilled  water. 

The  Titration  Methods,  which  consist  in  determining  the  quantity  of  an 
acid  or  alkaline  solution  of  a  given  strength  to  be  added  to  the  liquid  under 
examination,  in  order  to  modify  the  colour  of  an  indicator,  merely  give  the 
potential,  and  not  the  actual,  reaction  of  the  fluid.  Apart  from  errors  due  to 
the  nature  of  the  indicator,  it  must  be  remembered  that  not  only  the  quantity 


96  PHYSIOLOGY  CHAP. 

of  free  H  -f  and  OH  -  ions  remaining  in  the  fluid,  but,  further,  the  quantity 
of  H  +  and  OH  —  set  free  in  consequence  of  the  modifications  of  chemical 
equilibrium  between  non -dissociated  and  associated  molecules,  are  determined. 
The  titration  methods  most  commonly  employed  to  estimate  the  alkalinity 
of  the  blood  are  as  follows  : — 

1.  Zuntz  neutralised  the  alkalinity  of  the  blood  by  a  titrated  solution  of, 
phosphoric  acid,  1  c.c.  of  which  corresponds  to  OO05  grin,  of  sodium  carbonate. 
Litmus-paper  is  used  as  the  indicator.     Lassar,  on  the  other  hand,  employs  a 
decinormal  solution  of  tartaric  acid  (7 '5  grins,  of  acid  per  litre). 

2.  Landois  adopts  the  decinormal  solution  of  tartaric  acid,  and  a  perfectly 
neutral,  saturated  solution  of  sodium  sulphate.     As   indicator  he  uses   the 
finest  litmus-paper.     With  these  two  solutions  ten  mixtures  are  made  in  the 
following  proportions  :— 

I.     10  parts  -1Q  tartaric  acid  to  100  parts  saturated  sol.  NaS04. 

II.     20  „  „  90  „  „ 

X.  100  „  „  10  „  „ 

The  first  mixture  is  then  aspirated  to  a  distance  of  8  nun.  along  a 
graduated  pipette  made  of  a  glass  tube  1  mm.  in  diameter,  and  the  blood  to  a 
distance  of  16  mm.,  i.e.  8  mm.  of  each  fluid.  This  mixture  is  emptied  into 
a  watch-glass  and  the  reaction  tested.  Each  successive  mixture  is  employed 
in  the  same  way  until  the  alkaline  solution  becomes  acid.  The  degree  of 
alkalinity  corresponding  to  the  several  mixtures  is  as  follows  : — 

I.  =  0-036  per  cent  NaOH.  VI.  =  0-216  per  cent  NaOH. 

II.  -0-072         „            „  VII. -0-252 

III.  =0-108         „            „  VIII.  =  0-288 

IV.  =0-144         „            „  IX.  =0-324 
V.=  0-180         „            „  X.  =  0-360 

Jaksch    has    modified  Landois'  method    in  practice  as  follows.     He    too 

employs  a  solution  of  ^  tartaric  acid  and  a  concentrated  solution  of  sodium 

sulphate.     He  dilutes  the  first  solution  10  and  100  times,  making  solutions  of 

--  and  -  —  tartaric  acid  respectively.     These  solutions  are  mixed  with  the 

solution  of  sodium  sulphate  in  eighteen  mixtures,  which  contain  : — 

I.  0-9  c.c.  10Q  acid  with  O'l  c.c.  of  NaS04. 

II.  0-8  „         0-2 

IX.  0-1  ,,  „         0-9 

X.  0-90.0.^         „         0-1 
XL  0-8  „  „         0-2 

O'l  c.c.  of  blood  is  dropped  into  each  watch-glass,  stirred  up,  and  the  reaction 
tested  with  litmus-paper.  The  solutions  correspond  to  the  following  degree 
of  alkalinity  of  the  blood  :— 

I.  0-360  NaOH  in  100  grms.  of  blood. 

II.  0-320 

III.  0-250 

IX.  0-040 

X.  0-036 

XVIII.  0-004 

The  actual  reaction  of  the  blood  is  measured  by  the  Electrometric  Method 
(concentration  cell).  Particulars  will  be  found  in  any  modern  text-book  of 
physics. 


iv  THE  BLOOD :   FOKMED  CONSTITUENTS  97 

The  blood  has  the  highly  important  property  of  coagulating 
spontaneously.  In  a  few  moments  (3-12  minutes  for  human 
blood)  after  it  has  been  taken  from  the  blood-vessels  it  is  trans- 
formed into  a  gelatinous  mass,  which  assumes  the  shape  of  the 
vessel  that  receives  it.  It  is  the  formation  of  this  clot  which 
checks  the  continuation  of  haemorrhage  in  small  injured  vessels 
which  would  otherwise  lead  to  the  death  of  the  animal.  Clotting- 
depends  on  the  formation  and  separation  of  a  protein  from  the 
plasma,  i.e.  fibrin  (which,  as  we  shall  see,  does  not  pre-exist  as  such) 
in  the  form  of  a  fibrillar  reticulum  of  such  excessive  fineness,  that 
it  encloses  in  its  meshes  not  merely  the  whole  of  the  corpuscles, 
but  also  the  entire  liquid  portion  of  the  blood.  This  fact  appears 
the  more  marvellous  when  we  consider  that  the  amount  of  fibrin 
formed  during  coagulation  never  exceeds  1  per  cent  of  the  mass 
of  blood,  but  is  more  often  represented  by  a  fraction,  O4  per  cent, 
of  this,  and  may  even  fall  to  the  minimum  of  O'l  per  cent.  The 
separation  of  the  fibrin  from  the  mass  of  blood  can  be  effected  by 
prolonged  washing  of  the  clot  (Malpighi,  1666),  or  by  whipping 
the  freshly-extracted  blood  (liuysch,  1707).  In  this  last  case  the 
fibrin  clings  to  the  rod  used  for  whipping  as  a  fibrous,  elastic, 
whitish  mass ;  and  blood  thus  defibrinated  is  incapable  of  clotting. 

From  the  clot  containing  the  whole  mass  of  blood  a  yellowish 
fluid  gradually  separates  out  in  consequence  of  the  physical 
retraction  of  the  fibrous  reticulum,  the  so-called  serum,  which 
represents  that  part  of  the  plasma  that  remains  liquid  after 
coagulation.  When  all  or  nearly  all  this  serum  has  separated  out 
from  the  clot,  the  latter  is  seen  to  be  considerably  diminished  in 
volume,  though  it  still  keeps  the  form  of  the  vevssel.  The  clot 
thus  reduced  by  the  separation  of  the  plasma  is  sometimes  termed 
the  crassamentum. 

In  blood  which  has  been  rendered  incoagulable  by  defibrina- 
tion,  the  red  corpuscles,  being  heavier  than  the  serum,  tend  to  fall 
to  the  bottom  of  the  vessel,  so  that  an  almost  transparent  upper 
layer  is  formed  by  degrees,  consisting  principally  of  serum,  with 
an  opaque  lower  layer  formed  almost  exclusively  of  the  mass  of 
corpuscles.  The  separation  of  the  serum  from  the  corpuscles  is 
effected  with  maximal  speed  and  perfection  by  the  Centrifuge, 
which  can  be  performed  with  the  elegant  little  model  represented 
in  Fig.  25. 

If  coagulation  is  delayed  in  blood  newly  drawn  from  the 
veins  (as  is  often  observed  in  human  blood  during  inflammatory 
diseases,  and  normally  in  horses'  blood)  there  is  again  a  partial 
separation  of  the  plasma  from  the  red  corpuscles,  and  the  clot 
subsequently  formed  presents  a  greyish  superficial  layer  of  greater 
or  less  density,  known  as  the  buffy  coat,  or  crusta  phlogistica,  which 
consists  of  coagulated  plasma  mixed  with  leucocytes,  without  any 
red  corpuscles. 

VOL.  I  H 


98 


PHYSIOLOGY 


CHAP. 


V.  The  estimation  of  the  total  quantity  of  the  blood,  or  its 
relations  with  the  weight  of  the  animal,  presents  great  practical 
difficulties.  The  older  anatomists  held  very  exaggerated  views 
on  the  quantity  of  blood  in  man,  estimating  it  erroneously  by  the 
amount  of  injection  mass  that  can  be  forced  into  the  blood-vessels 
of  a  dead  body.  Far  too  low  values,  on  the  other  hand,  were 
obtained  at  a  later  period  by  the  method  of  completely  bleeding 
the  animal  (Herbst,  1822),  since  this  does  not  sufficiently  take 
into  account  the  quantity  of  blood  left  in  the  vessels,  which  may 
vary  considerably  in  different  cases. 


FIG.  25.— Hedin's  small  centrifuge.  By  means  of  three  cogged  wheels  enclosed  within  1,  2,  3,  each 
turn  of  the  handle  is  multiplied  100  times  from  the  axis  A,  the  apex  of  which  carries  a  cross- 
piece,  with  the  test-tube  holders  pp,  which  are  kept  horizontal  during  the  rotation. 

A  better  method  is  that  carried  out  by  Lehmann  and  Ed. 
Weber  on  two  criminals  (1853).  They  weighed  the  individuals 
before  and  after  decapitation,  and  from  the  difference  in  weight 
estimated  the  mass  of  blood  lost  by  bleeding.  They  took  a  sample 
of  this  blood.  They  then  injected  water  through  the  arteries  of 
the  trunk  and  head,  until  it  flowed  almost  colourless  from  the 
veins,  and  lastly  determined  the  weight  of  the  solids  contained 
in  the  blood  and  in  the  washings.  From  these  determinations 
they  calculated  the  quantity  of  blood  left  in  the  body  after 
decapitation. 

It  is  obvious  that  this  method  must  give  too  high  a  result. 
The  introduction  of  water  into  the  vessels  must  extract  not  only 


iv  THE  BLOOD:   FOKMEI)  CONSTITUENTS  99 

the  fixed  constituents  of  the  blood  remaining  in  the  system,  but 
also  such  as  have  penetrated  by  the  lymphatic  system  and  by 
diffusion  from  the  tissues,  during  and  soon  after  the  bleeding. 
In  one  of  the  criminals,  who  weighed  60,540  grins.,  the  mass  of 
the  blood  weighed  7520  grins.,  i.e.  one-eighth  of  the  body-weight. 
More  exact  results  were  obtained  with  the  chromometric 
method,  which  is  based  on  the  colouring  properties  of  the  blood 
pigment  (haemoglobin).  It  was  first  employed  by  Welcker  (1854) 
and  was  perfected  later  by  Gscheidlen  (1873).  A  little  normal 
blood  is  first  drawn  from  the  animal  and  weighed ;  the  whole  of 
the  blood  that  can  be  extracted  by  bleeding  is  then  collected ; 
that  left  behind  is  subsequently  washed  out  of  the  system  by 
irrigating  with  a  stream  of  isotonic  (0*60-0 '55  per  cent)  salt 
solution  ;  then,  after  removing  the  contents  of  the  gastro-iutestinal 
canal,  gall  bladder  and  urinary  bladder,  the  viscera  are  minced  up 
and  soaked  for  several  hours  in  the  saline  fluid  used  for  washing ; 
lastly,  the  washings  are  mixed  with  the  mass  of  blood  obtained 
by  bleeding.  The  blood-content  is  calculated  from  the  coloured 
liquid  obtained,  after  determining  the  quantity  of  saline  that 
must  be  added  to  the  weighed  specimen  of  blood  in  order  to  obtain 
the  same  degree  of  colour.  To  make  the  experiment  more  exact 
it  is  advisable  to  saturate  the  haemoglobin  with  carbon  monoxide, 
in  order  to  secure  the  same  degree  of  colour  in  both  mixtures. 

The  calculation  for  determining  the  quantity  of  blood  contained  in  the 
body  is  very  simple  : — If  a  is  the  quantity  of  blood  extracted  in  the  first 
bleeding,  x  the  quantity  of  blood  left  in  the  body,  b  the  quantity  of  physio- 
logical saline  employed  to  wash  out  the  vascular  system  and  organs  of  the 
animal,  c  the  quantity  of  physiological  saline  necessary,  to  make  the  colour 
of  the  blood  a  equal  to  that  of  the  blood  x,  plus  the  fluid  b  (a  quantity  which 
is  known  to  us,  and  which  we  may,  to  simplify  matters,  denote  as  d)  ;. 
it  is  easy  to  calculate  the  quantity  of  blood  x  according  to  the  following 
equation  : — 

a  4-  c  :  a  :  :  d  :  x 

and  therefore  x-=a —  •• 

a  +  c 

Having  thus  determined  the  value  x,  we  can  at  once  arrive  at  the  total 
volume  of  the  blood  by  adding  the  first  portion  a  extracted  in  the  pre- 
liminary bleeding  to  x  :  if  we  then  multiply  the  volume  of  blood  by  its 
specific  weight,  we  obtain  the  absolute  weight  of  blood,  the  relation  of  which 
to  the  total  body-weight  of  the  animal  has  finally  to  be  calculated. 

Welcker  came  to  the  conclusion  that  the  mass  of  the  blood 
varies  in  dogs  from  7  to  9  per  cent  of  the  body-weight,  in  rabbits 
from  5  to  9  per  cent.  Bischoff  (1855),  who  applied  these  methods 
to  the  bodies  of  two  criminals,  obtained  results  which  approxi- 
mated closely  to  those  obtained  by  Welcker  for  dogs  (7*1  to  7'7  per 
cent).  Assuming  that  in  man  the  blood  averages  ^  of  the  body- 
weight,  there  would  be  5  kilograms  of  blood  in  an  individual  of  65 
kilograms  body- weight. 

VOL.  I  H  a 


100  PHYSIOLOGY  CHAP. 

It  goes  without  saying  that  the  quantity  of  blood  must  vary 
with  the  constitution,  sex,  age,  state  of  nutrition,  and  with  many 
other  functional  or  purely  individual  factors.  Clearly,  lymphatic 
individuals  and  those  whose  fatty  tissues  (which  are  poorest  in 
blood)  are  strongly  developed,  must  have  a  considerably  lessf 
quantity  of  blood  than  other  individuals  in  whom  muscular 
tissues  which  are  richly  irrigated  with  blood  predominate.  The 
former  may  be  relatively  termed  anaemic,  the  latter  plethoric. 

VI.  The  morphological  study  of  the  blood  is  founded  on  micro- 
scopical observations,  which  show  the  presence  of  three  distinct 
elements — lied  Corpuscles  (Erythrocytes  or  Haemacytes),  White 
Corpuscles  (Leucocytes),  and  Platelets  (Hayeni's  Haematoblasts). 

The  Erythrocytes  are  in  the  form  of  biconcave  discs,  non- 
nucleated  and  round  in  all  mammals  (save  the  camel  and  the  llama, 


FIG.  26.— Form  and  relative  size  of  erythrocytes  of  different  animals,  viewed  from  the  'surface. 
1.  Erythrocyte  of  musk-deer ;  2,  goal;  3,  marmot;  4,  llama;  •'>.  man;  <],  pigeon;  7,  tench; 
8,  lizard  ;  9,  frog ;  10,  proteus. 

in  which  they  are  elliptical) ;  nucleated  and  elliptical  in  birds, 
reptiles,  amphibia  and  fishes  (Fig.  26).  The  red  corpuscles  of 
man  have  a  diameter  of  7-8  ^  and  a  depth  of  1'7  /x ;  in  other 
mammalian  animals  they  are  even  smaller;  in  birds  and  the 
lower  vertebrates  they  are  much  bigger  (21  /x  in  frog,  29  /x  in 
Triton,  58  /x  in  Proteus).  Viewed  from  above,  and  isolated,  they 
are  greenish-yellow  in  colour ;  seen  from  the  side  as  a  rouleau  of 
discs,  they  are  red  (Fig.  27) ;  to  them  the  blood  owes  its  char- 
acteristic colour,  and  they  render  it  opaque.  They  are  soft, 
almost  gelatinous  in  consistency — hence  they  easily  change  their 
shape ;  but  they  are  perfectly  elastic,  and  recover  their  original 
form  directly  the  contracting  force  ceases  to  act  on  them. 

Pted  corpuscles  may  be  divided,  according  to  their  affinity  for 
staining,  into  orthochrornatic  and  polychromatic  (Ehrlich).  The 
orthochromatic  are  the  most  numerous,  and  stain  with  aurantia 
and  eosin.  The  polychromatic,  which  are  much  less  frequent, 
take  up  fuchsin  when  they  are  stained  with  tri-acid ;  with  eosin- 
methylene-blue  they  stain  violet,  etc.  Red  corpuscles  are  classified 


iv  THE  BLOOD:  FOKMED  CONSTITUENTS          101 

according  to  their  form  and  size  (distinctions  which  concern  the 
pathologist)  into  normal  erythrocytes,  micro-  and  macrocytes, 
and  poikilocytes  (pear-shaped,  rod -shaped,  etc.).  Again  there 
are  red  corpuscles  which  exhibit  granules  of  different  si/es  and 
shapes  in  their  protoplasm,  and  which  will  stain  with  all  the 
basic  dyes  (basophile  granulation).  On  changing  the  stains,  the 
figures  produced  assume  quite  different  forms ;  this  shows  that 
the  figures  that  we  see  do  not  correspond  exactly  with  the  pre- 
existing arrangement  of  the  chromatic  substance,  but  depend  on 
the  different  physico-chemical  actions  exercised  by  each  individual 
colouring  substance  (Cesaris  Demel).  The  significance  of  these 
granules  is  uncertain ;  by  some  they  are  considered  to  be  the 
remains  of  nuclei,  according  to  others  they  are  protoplasmic 
formations. 


FIG.  27.— Red  blood-corpuscles  of  man.    (Magnification,  650  diameters.)    Some  are  seen  flat,  others 
in  profile,  the  majority  are  disposed  in  rouleaux. 

Although  Schultze  has  described  active  movements  of  the 
protoplasm  in  the  nucleated  erythrocytes  of  the  chick,  it  is  very 
doubtful  whether  the  red  corpuscles  of  mammalia  are  capable  of 
expanding  and  contracting  in  the  medium  in  which  they  normally 
live.  When,  however,  they  are  taken  out  of  the  vessels,  and  cooled 
or  warmed,  or  excited  by  induction  shocks ;  when  the  degree  of 
concentration  of  the  plasma  in  which  they  float  is  altered  by  the 
addition  of  water  or  of  saline  solutions ;  when  they  are  brought  in 
contact  with  extraneous  chemicals, — they  readily  change  their  shape, 
assuming  a  mulberry-like  or  even  prickly  (crenate)  appearance, 
and  extending  or  retracting  different  segments  of  their  protoplasm, 
as  if  undergoing  amoeboid  movements.  The  former  changes  are 
the  effect  of  altered  osmotic  conditions,  the  latter  are  probably 
to  be  regarded  as  active  movements  (Figs.  28  and  29). 

The  capacity  of  erythrocytes  for  active  movements  in  certain 
special  abnormal  conditions  is  confirmed  by  the  observations  of 
A.  Cavazzani.  He  noticed  that  when  blood  was  collected  in  an 
isotonic  or  hypotonic  solution  of  sodium  chloride,  to  which  potassium 


102  PHYSIOLOGY 


CHAP. 


ferrocyanide  or  a  highly  dilute  solution  of  potassium  sulpho- 
cyanide  had  been  added  in  the  proportion  of  about  1  per  1000, 
and  then  examined  under  the  microscope  at  a  temperature  of 
35-37°  C.,  the  erythrocytes  of  man  and  other  mammalia  (not 
of  birds  and  batracians)  put  out  delicate  prolongations  like  cilia, 
the  rapid  vibratory  movements  of  which  enable  the  corpuscles 
to  oscillate,  rotate,  or  move  forward.  These  cilia-like  pseudopodia 


*  #  •  O 


FIG.  28.  —  Successive  effects  upon  erythrocytes  of  discharge  from  a  Leyden  jar.  (Rollett.)  a, 
normal  erythrocyte  ;  b,  rosette  form  ;  c,  mulberry  form  ;  <1,  prickly  form  ;  e,  rounded  and 
swollen  erythrocyte  ;  /,  ghost. 

rise  from  the  smooth  surface  of  the  erythrocytes,  and  vary  in 
length  and  number.  Their  movements  of  expansion  and  retraction 
are  slow  and  limited.  If  a  drop  of  solution  of  cocaine  hydrochloride 
is  added  to  the  preparation,  the  erythrocytes  resume  their  former 
shape  in  a  few  moments.  If  washed  free  of  the  cocaine,  and 
treated  afresh  with  the  ferrocyanide,  they  may  resume  their 
ciliated  aspect. 

Since,  according  to  the  researches  of  Albertoni,  cocaine  paralyses 
protoplasm,  it  follows  that  the  changes  of  form  exhibited  by  the 

erythrocytes  under  the  influence  of  potas- 

a      5        c  ^     sium  ferrocyanide  must  be  considered  as 

fl      Q      ft      @   \^)    active  movements  of  the  protoplasm.    Ery- 

throcytes have  a  fairly  tenacious  vitality. 

When  taken  out  of  the  blood  -  vessels  and 
a  C^  reinjected,  they  survive  after  as  much  as 
^^  4-5  days,  but  only  provided  they  are  kept 

FIG.  29.—  a,  Successive  effects  upon     •       •  Tf   ViPq4-p^    fn   KO0  p      flipv  rlio    an/1 

erythrocytes  of  water  (Schafer)  ;    *      lce-  teateu    tO  OZ     1^.,  Uiey  QIC    ana 

b,  action  of  a  solution  of  salt  ;  break    up   when    reintroduced    into    the 

c,  action  of  tan  me  acid.  .  -.* 

circulation.     If  transfused  into  animals  ol 

a  different  kind  they  do  not  survive,  but  degenerate  and  disin- 
tegrate more  or  less  rapidly,  owing  to  the  heterogeneous  plasma 
with  which  they  are  brought  in  contact. 

The  direct  enumeration  of  the  corpuscles  contained  in  a  given 
quantity  of  blood  (1  c.mm.)  was  correctly  performed  for  the  first 
time  by  Vierordt  and  Welcker  (1854),  the  results  they  obtained 
having  been  confirmed  by  more  recent  observers.  The  method 
and  apparatus  have  been  perfected,  and  are  now  practical  and 
easily  applicable  for  clinical  purposes.  We  must  here  confine 
ourselves  to  naming  those  of  Malassez,  Hay  em,  and  Thoma-Zeiss. 

Haemacytometer  of  Thoma-Zeiss.  In  order  to  count  blood  -corpuscles  with 
the  Thoma-Zeiss  apparatus,  the  point  of  the  capillary  glass  pipette  (Fig.  30, 
I)  is  dipped  into  the  drop  of  blood  to  be  examined,  which  is  obtained  by 


IV 


THE  BLOOD:   FOKMED  CONSTITUENTS 


103 


pricking  the  finger  with  a  needle.  A  column  of  blood  is  aspirated  by  means 
of  the  rubber  tube  to  division  0'5  or  1  of  the  pipette,  and  after 'quickly 
drying  the  lower  end,  the  bulb  of  the  pipette  is  filled  up  to  the  figure  101 
(which  expresses  its  capacity  in  c.mm.)  with  3  per  cent  salt  solution,  or  with 
Pacini's  fluid  as  modified  by  Hayem  and  Gram  (corrosive  sublimate  0'5  grin., 
sodium  sulphate  5  grms.,  sodium  chloride  2  grms.,  distilled  water 
200  grms.).  It  is  then  sufficient  to  shake  the  pipette  for  a  few 
moments  in  order  that  the  glass  ball  (a),  which  is  loose  inside 
the  bulb,  may  mix  the  blood  with  the  salt  solution,  and  make 
the  fluid  homogeneous.  As  the  division  0'5  corresponds  exactly 
to  -y^  of  the  total  capacity  of  the  bulb,  and  the  figure  1 
exactly  to  T^y,  we  know  that  the  mixture  obtained  is  in  the 
ratio  of  1 : 200  or  1 : 100. 

The  counting  is  done  upon  a  carrier  (II)  of  thick  glass 
with  a  groove  (6),  the  bottom  of  which  is  divided  by  lines  cut 
with  a  diamond  into  400  minute  squares  (as  is  shown  in  III). 
Into  this  groove,  the  capacity  of  which  is  O'l  c.mni.,  a  drop  of 
the  blood  solution  contained  in  the  bulb  of  the  pipette  is  intro- 
duced, care  being  taken  to  drive  out  the  liquid  contained  in  the 
capillary  portion,  which  has  not  been  mixed  with  the  blood. 
When  the  drop  is  placed  in  the  groove,  a  cover  glass  (a)  is 
quickly  applied,  and  after  letting  the  preparation  rest  for  a  few 
minutes  upon  a  perfectly  horizontal  surface,  in  order  that  the 
red  corpuscles  may  be  spread  evenly  upon  the  floor  of  the  groove, 
the  counting  is  undertaken  under  a  magnification  of  200 

II 


0  « 


ni 

FIG.  30. — Thoina-Zeiss  Haemacytometer.     I,  Graduated  pipette  (Potain's  mixer) ;  II,  cell  for 
counting  corpuscles,  side  view  ;  III,  squared  divisions  of  bottom  of  haemacytometer. 

diameters.  The  number  of  the  corpuscles  counted  is  divided  by  the  number 
of  squares  examined,  which  should  never  be  less  than  200 ;  thus  obtaining 
the  average  of  the  red  corpuscles  contained  in  each  square,  which  represents 
pAnr  c.mm.  Hence,  if  we  wish  to  know  the  number  of  corpuscles  in  c.mm. 
it  is  only  necessary  to  multiply  the  number  found  first  by  4000,  and  then 
by  100  or  200,  according  as  the  blood  has  been  diluted  iOO  or  200  times. 
To  take  a  practical  example  : — If  1225  corpuscles  are  counted  in  250  squares, 
VOL.  I  H  1) 


104  PHYSIOLOGY  CHAP. 

and  the  blood  has  been  diluted  200  times,  1  c.mm.  of  blood  will  contain 

1 99  r, 

£  x  4000  x  200  =  3,920,000  red  corpuscles. 
250 

The  white  blood-corpuscles  can  be  counted  at  the  same  time ;  but  if  a 
separate  enumeration  is  desired  for  the  sake  of  accuracy,  the  blood  must  be'' 
agitated  with  a  0*3  per  cent  solution  of  acetic  acid,  in  which  the  red  corpuscles 
will  dissolve  while  the  white  remain  intact. 

Hedin's  Haematocrit  is  an  apparatus  for  determining  the  total  volume  of 
red  corpuscles  in  100  parts  of  blood.  It  consists  of  a  small  centrifuge  (Fig.  25, 
p.  98)  and  of  two  graduated  tubes  (a,  «',  Fig.  31).  The  determination  is 
carried  out  as  follows  : — A  small  quantity  of  Miiller's  fluid  (sodium  sulphate  1 
grm.,  bichromate  of  potash  2  grins.,  distilled  water  100  grins.)  is  taken  up  with 
a  pipette,  and  dropped  into  a  small  porcelain  dish.  The  finger  is  then  pricked 
with  a  lancet  so  as  to  obtain  a  large  drop  of  blood.  With  the  same  pipette  a 
quantity  of  blood  equal  to  the  quantity  of  M  tiller's  fluid  is  taken  up,  and 
emptied  into  the  same  dish.  The  two  fluids  are  then  thoroughly  mixed  with 
a  glass  rod,  with  the  double  object  of  retarding  the  coagulation  of  the  blood 
(the  mixture  will  not  clot  under  half  an  hour)  and  of  fixing  the  red  corpuscles 
in  their  natural  size.  The  graduated  tube  is  then  filled  with  the  mixture 
thus  obtained,  by  taking  up  the  fluid  from  the  dish  directly  into  the  tube, 


Fin.  31.— Hedin's  Haematocrit— substitute  for  test-tube  holder  of  Fig.  ~2'>,  p.  us.  a,  a',  Graduated 
tubes,  kept  in  the  hollows  prepared  for  them  by  the  presence  of  two  elastic  springs;  6,  ?/, 
small  metal  rods  that  compress  the  spirals  in  loosening  or  tightening  the  tubes. 

which  has  previously  been  fitted  with  a  rubber  tube  furnished  with  a  mouth- 
piece. The  tubes  have  a  calibre  of  1  sq.  mm.,  and  are.  divided  into  50  parts. 
The  filled  tubes  are  then  fixed  to  a  horixontal  holder  (shown  in  Fig.  30),  which 
replaces  the  test-tube  holders,  pp,  of  the  centrifuge  (Fig.  25),  care  being  taken 
not  to  lose  any  of  the  fluid.  They  are  now  centrifuged  for  five  to  seven 
minutes  with  a  velocity  of  80  turns  per  minute  of  the  handle  of  the  apparatus, 
which  corresponds  to  8000  revolutions  of  the  tubes,  until  the  red  corpuscles 
separate  out  into  a  compact  and  well-marked  column,  the  volume  of  which 
will  not  shrink  further.  Since  the  tubes  have  very  thick  walls,  and  the 
graduation  is  cut  on  the  surface,  errors  may  occur  in  the  reading  which  are 
due  to  the  different  positions  of  the  reading  eye.  The  inventor  of  the 
apparatus  has  calculated  this  error  as  equal  to  0'2  degree  of  the  scale,  and 
to  avoid  it  suggests  that  the  reading  be  carried  out  by  looking  along  a  glass 
plate  held  at  right  angles  to  the  tube.  From  the  volume  found,  the  volume 
of  corpuscles  in  100  parts  of  blood  can  be  determined  by  multiplying  the 
volume  of  the  column  of  blood-corpuscles  by  4.  As  two  determinations  of 
the  volume  of  the  erythrocytes  are  made  at  the  same  time,  these  form  a 
reciprocal  control 

Since  the  total  volume  of  the  mass  of  corpuscles  is  proportional  to  the 
relative  number  of  the  erythrocytes,  this  method  can  be  substituted  for  that 
of  Thoma-Zeiss,  which  takes  much  longer  to  carry  out. 

Many  series  of  determinations  on  the  relative  mass  of  corpuscles 
have  been  worked  out,  on  man  as  well  as  animals,  in  order  to 


iv  THE  BLOOD :   FOKMED  CONSTITUENTS          105 

ascertain  the  variations  due  to  age,  sex,  constitution,  functional 
state  of  the  body,  various  morbid  conditions  of  the  blood,  and  so 
on.  As  an  average  it  may  be  taken  that  1  c.mrn.  contains  5,000,000 
red  corpuscles  in  a  man,  4,500,000  in  a  woman ;  that  they  are 
more  abundant  in  venous  than  in  arterial  blood ;  less  abundant 
in  adolescents  than  in  adults,  more  numerous  in  new-born  infants 
than  in  the  mother ;  that  all  the  influences  that  induce  a  marked 
loss  of  water  in  the  body  increase  their  number,  while  a  high 
intake  of  water  diminishes  them ;  that  they  multiply  with  every 
improvement  in  the  external  and  internal  conditions  of  life,  while 
poor  food  and  a  vast  number  of  morbid  conditions  tend  to  reduce 
them. 

It  is  remarkable  that  the  lowering  of  atmospheric  pressure 
on  high  mountains  produces  a  considerable  increase  in  the  number 
of  erythrocytes  (Viault).  The  same  effect  has  been  observed  in 
mice  on  rubbing  their  skin  with  croton  oil,  and  on  prolonged 
exposure  to  strong  electric  light  (Kronecker).  It  should  also  be 
noted  that  not  merely  scanty  nutrition,  but  even  an  absolute  fast 
of  thirty  days,  produces  no  marked  variation  in  the  number  of 
the  erythrocytes  (Luciani).  Obviously  the  relative  quantity  of 
corpuscles,  which  depends  upon  the  degree  of  concentration  and 
amount  of  water  contained  in  the  blood,  can  rarely  yield  a  safe 
conclusion  as  to  the  absolute  quantity  to  be  found  in  the  total 
mass  of  blood. 

The  volume  and  surface  of  the  erythrocytes  have  been 
approximately  determined,  by  using  models  of  enormous  magnifica- 
tion ;  5,000,000  corpuscles  are  found  to  have  a  volume  of  about 
\  c.mm.  and  a  surface  of  610  sq.  mm. 

The  specific  gravity  of  erythrocytes  is,  as  already  stated, 
greater  than  that  of  plasma  and  serum  (rOSS-TlOS).  The  weight  of 
the  corpuscles  contained  in  100  grins,  of  defibrinated  blood  is  not 
far  short  of  that  of  the  serum,  averaging  a  weight  of  48  grms.  in 
man  and  35  grins,  in  woman.  Given  a  man  of  78  kilograms, 
whose  blood  amounts  to  •£%  of  his  body-weight,  the  total  weight 
of  the  erythrocytes  would  be  about  2  kgrm.,  with  a  total  surface 
of  some  3840  sq.  metres. 

VII.  The  pigment  which  colours  the  erythrocytes  is  a 
compound  of  highly  complex  chemical  structure,  known  as 
Haemoglobin.  Under  physiological  conditions  it  is  entirely  absent 
from  the  plasma,  and  exclusively  saturates  the  colourless  spongy 
mass  of  the  corpuscle,  termed  by  Eollet  the  stroma.  This  fact 
suggests  that  it  may  be  in  chemical  combination  with  one  of  the 
constituents  of  the  stroma,  perhaps  with  the  lecithin  (Hoppe- 
Seyler).  But  the  most  certain  and. -most  important  property  of 
the  pigment,  and  that  on  which  the  capital  function  of  the 
erythrocytes  depends,  is  its  affinity  for  oxygen,  with  which  it 
combines  as  soon  as  the  partial  pressure  of  the  gas  reaches  a 


106  PHYSIOLOGY  CHAP. 

certain  value,  forming  oxy haemoglobin,  which  with  a  fall  of  the 
partial  pressure  is  again  reduced  to  haemoglobin.     It  prevails  in 
the    form   of    oxyhaemoglobin   in    arterial,  as   haemoglobin   and 
oxy  haemoglobin  in  venous,  exclusively  as  haemoglobin  in  asphyxia  1 '" 
blood. 

There  are  many  physical  and  chemical  means  by  which  the 
pigment  is  easily  separated  from  the  stroma  of  the  corpuscles  and 
dissolved  in  the  plasma.  Among  the  physical  methods  are 
warming  of  the  blood  to  50-60°  C.,  repeated  freezing  and  thawing, 
the  discharges  of  a  Leyden  jar,  induced  or  galvanic  currents; 
among  the  chemical  methods,  simple  dilution  with  water,  addition 
of  ether,  chloroform,  dilute  alcohol,  acid  or  alkaline  solutions,  bile, 
heterogeneous  serum,  etc.  By  using  sodium  chloride  solutions  of 
various  concentrations,  different  degrees  of  diffusibility  of  pigment 
can  be  detected  in  different  corpuscles  and  different  individuals. 

According  to  Winter's  researches  (1896),  the  isotonic  solution, 
i.e.  that  which  has  the  same  degree  of  molecular  concentration  as 
the  corpuscles  (and  therefore  produces  no  disturbance  of  osmotic 
relations  and  no  diffusion  of  haemoglobin  in  the  plasma);  is  repre- 
sented by  a  solution  of  about  0'91  per  cent  NaCl  in  distilled 
water. 

In  proportion  as  the  pigment  separates  out  from  the  stroma, 
the  corpuscles  grow  pale,  and  finally  change  into  roundish, 
colourless,  almost  transparent  bodies  which  have  been  termed 
ghosts  (JBlutschatten),  because  they  are  almost  invisible.  They 
stain  brown  with  iodine  and  can  thus  be  detected. 

In  order  to  study  the  chemical  composition  of  the  stroma  of 
the  erythrocytes  a  large  mass  of  blood  corpuscles  must  be  collected, 
separated  from  the  plasma,  washed  with  dilute  solution  of  sodium 
chloride,  and  completely  freed  from  haemogloblin  by  the  addition 
of  5-6  volumes  of  distilled  water.  By  this  treatment  all  is 
removed  save  the  stroma,  which  forms  a  gelatinous  mass  and  can 
be  separated  by  filtration  from  the  watery  solution. 

The  small  amount  of  matter  remaining  on  the  filter  dissolves 
in  dilute  salt  solution,  and  gives  all  the  reactions  of  globulin. 
But  the  stromata  separated  from  the  erythrocytes  of  birds  contain, 
in  addition  to  globulin,  a  considerable  quantity  of  nuclein,  derived 
from  the  nuclei  of  these  corpuscles  (Plosz,  Hoppe-Seyler).  Kossel, 
with  dilute  hydrochloric  acid,  also  extracted  a  substance  belonging 
to  the  albumose  group,  to  which  he  gave  the  name  of  histone. 

If  further  chemical  researches  prove  that  the  erythrocytes 
of  mammals  contain  no  nuclein,  this  would  be  an  additional 
proof  that  they  really  are  non-nucleated,  which  has  been  denied 
by  some  observers. 

An  ethereal  extract  of  a  mass  of  stromata  yields  the  other 
organic  components  of  protoplasm,  lecithin  and  cholesterin. 

The  inorganic  substances  of  the  stroma  consist  of  potassium 


IV 


THE  BLOOD :   FOKMED  CONSTITUENTS 


107 


phosphate  and   potassium    chloride ;    in   man,  and   a   few   other 
animals  only,  there  is  also  a  small  amount  of  sodium  chloride. 

The  water  content  of  the  erythrocytes  is  very  low  as  compared 
with  other  organs.  In  man  it  reaches  only  5  7 '7  per  cent,  while 
in  the  muscles  and  glands  it  amounts  to  75  per  cent  (Hoppe- 
Seyler). 

The  dry  substance  of  the  erythrocytes  consists  principally  of 
haemoglobin  (87-95  per  cent),  so  that  the  stroma  is  a  very  small 
amount  (13*5  per  cent).  For  the  total  quantity  of  the  blood, 
about  13*8  per  cent  haemoglobin  lias  been  calculated  for  man,  and 
about  12'6  per  cent  for  woman. 

Hoppe  -  Seyler  was  the  first  to  investigate  the  chemical 
properties  of  haemoglobin  (1860-71 )  and  to  recognise  that  although 
it  is  a  colloid  body,  it  is 
capable  of  crystallising  in 
different  forms  in  different 
animals,  all,  however,  belong- 
ing to  the  rhombic  system 
(with  the  exception  of 
squirrel's  blood,  which  crys- 
tallises in  hexagonal  plates ; 
Fig.  32).  To  obtain  crystals 
of  pure  haemoglobin,  they 
must  first  be  dissolved  in  the 
blood  by  freezing  and  gradual 
melting ;  the  blood  in  a  layer 
2  mm.  deep  is  then  allowed 
to  evaporate  slowly  in  a  flat, 
wide-bottomed  capsule. 

The  different  forms  of 
oxyhaemoglobin  crystals,  the 
different  quantities  of  water  of  crystallisation  which  they  contain, 
their  different  solubilities  and  different  resistance  to  decomposing 
agents,  in  short  the  varying  results  of  elementary  analysis,  all  point 
to  the  conclusion  that  oxyhaemoglobin  is  not  identical  in  different 
animals.  It  is  a  highly  complex,  iron-containing  protein,  the 
formula  of  which  was  determined  by  Hiit'ner  from  analysis  of 
the  haemoglobin  of  dogs'  blood.  Each  molecule  of  haemoglobin 
combines  with  a  molecule  of  oxygen  to  form  oxyhaemoglobin. 

Haemoglobin  has  a  greater  affinity  for  carbonic  oxide  than  for 
oxygen,  and  forms  with  it  carboxy haemoglobin,  which,  unlike 
oxyhaemoglobin,  doas  not  reduce  with  deoxidising  agents.  While 
carbonic  oxide  turns  out  oxygen,  the  latter  has  difficulty  in 
driving  carbonic  oxide  out  of  its  combination  with  haemoglobin. 
To  this  fact  is  due  (in  part,  if  not  wholly)  the  toxic  action  of 
carbon  monoxide. 

With  a  series  of  oxidising  agents,  particularly  with  nitrites, 


52. — Haemoglobin  crystals.    (Funke.)    «,  From 
man  ;  b,  guinea-pig ;  c,  squirrel. 


108 


PHYSIOLOGY 


CHAP. 


FIG.  33. — Haeiuiu  crystals.     (Preyer.) 


permanganate  of  potash,  potassium  ferricyanide,  active  oxygen, 
hydrogen  peroxide,  etc.,  haemoglobin  is  converted  into  methaemo- 
globin,  which  is  an  isomer  of  oxy haemoglobin,  but  in  which  the 
oxygen  is  more  closely  combined,  so  that  it  cannot  be  driven  out 
by  the  unaided  vacuum.  Methaemoglobin  can  also  be  formed  jn 

circulating  blood  by  the  excessive 
use  of  chlorate  of  potash  and 
other  substances  used  in  medicine 
in  recent  years  as  antipyretics. 

Haemoglobin  undergoes  spon- 
taneous decomposition  slowly 
under  the  influence  of  air  and 
water,  rapidly  as  the  effect  of 
acids  or  alkalies,  or  of  heating. 
Another  iron -containing  pigment 
is  thus  formed,  haemochromogen, 
which  oxidises  readily  in  the 
presence  of  oxygen  and  is  con- 
verted into  haematin,  which  gives 
a  brownish  colour  to  the  solution. 
Along  with  haernochrornogen  and 
haematin,  the  decomposition  of  haemoglobin  gives  rise  to  con- 
siderable quantities  of  acid  or  alkali  albumin,  according  as  acids 
or  alkalies  are  used  to  break  up  the  blood  pigment.  From  these 
facts  Hoppe-Seyler  regards  haemoglobin  as  a  protein,  which  con- 
sists of  an  albumin,  associated 
with  an  iron-containing  pigment, 
haemochromogen.  One  hundred 
parts  of  haemoglobin  contain 
ninety-six  parts  albumin  and  four 
parts  pigment.  Haemin  must 
be  noted  among  the  decomposi- 
tion products  of  blood  pigment  on 
account  of  its  great  practical  im- 
portance ;  it  crystallises  in  the 
form  of  small  rhombic  plates  or 
rods,  of  a  shining  brown  colour 
(Pig.  33).  Haemin  crystals  are 
of  great  importance  in  forensic 

medicine,      in      the      detection      Of        FK,   34.-Haematoidin  crystals.     (V.  Frey.) 

blood-stains.      A  trace  of  dried 

blood  suffices  to  obtain  them.  A  grain  of  sodium  chloride  is- 
added,  dissolved  in  a  few  drops  of  glacial  acetic  acid,  and  cautiously 
heated  over  a  spirit  lamp  until  gas  bubbles  are  formed. 

Haemin  is  haematin  hydrochloride,  and  to  obtain  pure  haematin 
it  is  necessary  to  start  from  this  combination.  It  is  a  sulphur-free 
compound,  but  is  richer  in  iron  than  haemoglobin.  When  treated 


iv  THE  BLOOD:   FOKMED  CONSTITUENTS          109 

with  sulphuric  acid,  the  haematin  loses  its  iron  and  takes  up  water, 
turning  into  haematoporphyrin,  an  iron -free  pigment  somewhat 
resembling  haemoglobin  in  colour. 

Another  iron  -  free  derivative  of  haemoglobin,  which  forms 
spontaneously  in  a  crystalline  form  in  the  corpora  lutea  and  in 
old  haeinorrhagic  foci,  is  haematoidin  (Virchow),  now  regarded  by 
chemists  as  identical  with  bilirubin,  one  of  the  principal  bile- 
pigments  (Fig.  34). 

,It  seems  clear  that  all  the  colouring  matters  of  bile  and  urine 
are  derived  from  successive  transformations  of  blood  pigment;  but 
with  the  exception  of  bilirubin,  which  forms  spontaneously,  only 
one  of  the  urinary  pigments,  urolilin,  has  at  present  been  produced 
artificially  from  haemoglobin  or  haematin. 

Many  of  the  pigment  substances  above  recorded,  haemoglobin, 
oxyhaemoglobin,  carboxyhaemoglobin,  methaemoglobin,  haeniochro- 
mogen,  haematin,  haematoporphyrin,  urobilin,  possess  the  important 
property,  when  examined  in  layers  of  known  thickness  and  con- 
centration, of  absorbing  well-determined  and  distinct  zones  of  the 
spectrum  in  aqueous  solutions,  acid  or  alkaline,  as  shown  in  Fig.  35. 
It  is  important  to  note  that  while  haemoglobin  shows  a  single 
absorption  band  between  the  Fraunhofer  D-  and  E  -  lines, 
oxyhaemoglobin  and  carboxyhaemoglobin  show  two  bands  that 
almost  coincide  in  the  two  cases,  lying  practically  within  the 
same  region  of  the  spectrum.  Apart  from  the  different  tint 
exhibited  by  oxy-  and  carboxyhaemoglobin,  the  former  being  the 
pinker,  they  can,  however,  readily  be  distinguished  by  adding  a 
reducing  substance,  e.g.  carbon  disulphide,  to  the  two  solutions, 
when  the  spectrum  of  oxyhaemoglobin  is  speedily  transformed 
into  that  of  haemoglobin,  while  the  spectrum  of  carboxyhaemo- 
globin undergoes  no  modification. 

To  determine  the  relative  quantity  of  haemoglobin  contained  in  a  given 
quantity  of  blood,  several  instruments  have  been  adopted.  The  simplest  and 
most  convenient  Haemoglobinometer  is  Gowers'  apparatus,  provided  with  a 
standard  solution  of  CO-haemoglobin.  The  method,  as  accurately  described 
by  Haldane,1  gives  extremely  good  results. 

For  more  accurate  quantitative  determination,  either  of  the  haemoglobin 
or  of  the  pigments  derived  from  it,  the  Spectro-Photometric  Method  must 
be  employed. 

This  method-  is  based  on  the  law  that  the  coefficient  of  extinction  of  any 
coloured  solution  is  (for  any  given  zone  of  the  spectrum)  directly  proportional 
to  its  concentration,  i.e.  C  :  E=C' :  E',  when  C  and  C'  indicate  the  correspond- 
ing coefficient  of  extinction,  By  coefficient  of  extinction  of  a  fluid  is  meant 
the. negative  logarithm  of  that  intensity  of  light  which  remains  after  it  has 
traversed  a  liquid  stratum  of  the  depth  of  1  c.c.  (Kriiss,  Kolorimetrie  u.-quantit. 
Spectmlanalyse,  1891). 

HC     V 

From  the  above  equation  it  follows  that  -—:=—;  this  ratio,  known  as 

&      si, 

that  of  absorption,  is  a  constant  for  the  same  colouring  substance.     Now,  if 


1  Journ.  of  Physiol.  xxvi.  497. 


PHYSIOLOGY 
D  E  b 


CHAP. 


6 


S 


9 


10 


Fia.  35. — Absorption-spectrum  of  blood-pigment  and  its  derivatives.  1,  Oxyhaemoglobin  ;  2,  haemoglobin  ; 
3,  methaemoglobin  and  haematin  in  acid  solution  ;  4,  haematin  in  alkaline  solution  ;  5,  haeinatoporphyrin 
in  acid  solution;  6,  haematoporphyrin  in  alkaline  solution  ;  7,  haemochromogen  in  alkaline  solution';  8, 
earboxyhaernoglobin  and  carboxyhaernochromogen ;  9,  sulpho-inethaemoglobin ;  10,  hydrobilirubin  and 
urebilin  in  acid  solution. 


IV 


THE  BLOOD:   FOKMED  CONSTITUENTS 


111 


the  absorption  ratio  be  represented  by  A,  the  coefficient  of  extinction  by  E, 
and  the  content  of  colouring  matter  in  1  c.c.  (calculated  in  grams)  by  C,  it 
follows  tkat  C  will  be  equal  to  A  x  E. 

The  most  exact  of  the  various  instruments  constructed  for  the  determination 
of  coefficients  of  extinction  is  that  of  Kriiss.  This  (as  shown  by  Fig.  36) 
resembles  an  ordinary  spectroscope  and  differs  from  the  spectre-photometers 
of  Vierordt,  Hiifner  and  others,  in  that  the  two  slits//'  (Fig.  38)  which  give 
the  two  spectra,  one  above  the  other,  enlarge  and  contract  in  both  directions 
with  a  single  movement  of  the  screws  V  and  V. 

To  use  this  apparatus,  fill  a  small  pipette  of  capillary  bore  with  blood  to  a 


FIG.  36. — Spectrp-photometer  of  Kriiss  viewed  as  a  whole.  The  extreme  end  of  the  eye-piece  is 
.shown  in  Fig.  37.  The  extreme  end  of  the  objective  is  shown  in  detail  in  Fig.  38.  The 
lettering  corresponds.  The  absorption-chamber  containing  the  solution  of  the  pigment,  to  be 
examined  is  shown  in  Fig.  39.  The  third  branch  x,  illuminated  by  a  gas  flame,  projects  the 
millimetre  scale  on  to  the  spectrum. 

given  capacity,  say  20  c.mm.  This  blood  must  be  rapidly  expelled  into  a 
small  beaker  in  which  a  measured  quantity  of  distilled  water  has  first  been 
placed,  so  that  the  blood  is  diluted  in  known  measure.  The  degree  of 
dilution  varies  with  the  greater  or  less  colouring  power  of  the  blood  to  be 
tested,  but  as  a  rule  the  ratio  of  1-200  is  preferred.  The  pipette  which  held 
the  blood  should  be  washed  out  several  times  with  the  water  used  for  dilution, 
and  the  liquid  must  be  agitated  till  it  is  homogeneous  in  colour.  The 
absorption  chamber  (Fig.  39),  which  is  a  crystal  cell  with  parallel  faces,  is 
then  filled,  and  a  cube  of  glass,  D,  of  the  exact  diameter  of  1  cm.,  introduced, 
to  which  the  name  of  Sclmltz'  cube  is  given.  The  two  absorption  spectra 
are  those  of  two  strata  of  the  same  fluid  differing  by  1  cm.  in  depth. 

The  extinction  coefficients  for  human  pxyhaemoglobin  have  been  deter- 
mined in  two  different  regions  of  the  spectrum,  i.e. 

D  32  E  -  D  54  E  and  D  63  E  -  D  24  E  ; 


112 


PHYSIOLOGY 


CHAP. 


ill  which  Hiifuer  has  determined  the  absorption  ratios  or  constants  for,  viz.  : 
0,001330  and  0,001000  respectively. 

The  limits  of  these  spectral  positions,  which  are  comprised  between  the 
Fraunhofer  D-  and  E- lines,  may  be  expressed   in  wave-lengths  by  means'/ 


FIG.  :57.— W,  Micrometer  screw,  divided  into  hundredths,  each  turn  of  which  displaces  the  index  of 
the  scale  S  by  one  division.  This  serves  to  regulate  and  measure  the  width  of  the  slit  /,  which 
can  be  carried  by  a  horizontal  movement  to  the  centre  of  the  eye-piece.  /,-,  Micrometer  screw 
divided  into  hundredths,  eacli  turn  of  which  displaces  the  index  of  a  scale  n  by  one  division. 
This  moves  the  eye-piece  by  an  angular  development  to  carry  it  to  any  given  region  of  the 
spectrum. 

of  the  table  published  by  Kriiss  (as  above  cited).  In  practice  they  can  be 
obtained  by  finding  011  the  illuminated  scale  of  the  spectrum  (Fig.  36,  s) 
the  values  corresponding  to  the  two  wave-lengths  calculated,  and  limiting 

the  spectral  region  which  these 
comprise;  by  the  horizontal  screw 
of  the  telescope  (Fig.  37),  and  that 
marked  W,  which  controls  the 
slit  /  of  the  eye-piece.  The  ab- 
sorption chamber  A  is  then  placed 
on  its  support  between  the  plane 
of  the  spectrum  and  the  source  of 
light,  taking  care  that  the  upper 
surface  of  the  cube  D  corresponds 
exactly  with  the  line  of  division 
between  the  first  and  second  slit, 
and  that  the  aperture  of  these 
corresponds  to  a  complete  turn  of 
the  screw :  a  turn  divided  into 
100  parts,  as  shown  on  the  scale 
affixed  to  the  screws  v  and  v'  in 
Fig.  38. 

On  then  looking  through  the 
F"Y   :     ~*Z'  r'  Mi?rom«ter  screw  di}'id«l   I"*?   instrument,  two  positions  of  the 

hundredths,  serves  to  widen  or  narrow  the  slit  /./,  4.  ill  i         •   'vi  i    i 

by  simultaneous  displacement  of  the  two  plates    spectrum  Will  be  Visible,  Olie  below 

that  confine  it.  the  other  :  one  is  brighter,  corre- 

sponding to  the  cube  of  Schultz, 
the  other  obscured  by  the  absorption  due  to  the  solution  of  oxyhaemoglobin. 

The  slit  corresponding  to  the  brighter  part  of  the  spectrum  is  then 
narrowed  until  it  assumes  the  same  tone  of  light  as  the  other,  and  the 
scale  on  the  screw  read  to  show  how  many  turns  were  required  to  produce 
uniform  obscurity.  From  this  number,  which  indicates  the  intensity  of  the 


l.e........a. 

...e  e... 

, 

B~    ft   (—} 
m^  —  \^i 

X 

f-/' 

•:'V.  .  o 

I 

.      „._  v^-ijij         r 

L 

..w._.xJj|.|      V^» 

-$^-^~ 

' 

%a. 

-"''''     ° 

_^^_  /*JV-  -X^V 

V^7          *<^/          ^7 

•"9  "0" 

e     e 

IV 


THE  BLOOD:   FORMED  CONSTITUENTS 


113 


light  remaining  after  tlie  luminous  rays  have  traversed  the  colouring  matter 
of  the  blood,  the  negative  logarithm  that  represents  the  extinction  co-efficient 
can  be  calculated,  and  this  must  be  multiplied  first  by  the  constant  of  the 
spectral  tone  obtained,  and  then 
by  the  degree  of  dilution  of  the 
blood.     Thus  it  is  calculated  how 
many  grams  of  haemoglobin  are 
contained  in  1  c.c.  of  blood. 

Practical  Example. — Let  the 
blood  under  examination  have 
been  diluted  200  times,  and  the 
first  spectral  region  be  that,  in 
which  the  constant  is  0-001330, 
the  intensity  of  the  remaining 
light  will  be  found  to  be  0-255  ; 
to  calculate  the  amount  of  oxy- 
haemoglobin  contained  in  1  c.c. 
of  the  blood,  multiply  0*001330 
by  200,  and  then  by  the  negative 
logarithm  of  0'255,  i.e.  by  0'5935. 
In  this  case  the  oxyhaemoglobin 
of  1  c.c.  of  blood  will  be  equal  to 
0-1578  grm. 

VIII.  The  White  Blood 

Or  LeUCOCyteS  are     FIG.  W.—A,  Absorption-chamber  with  parallel  faces; 
pnrl   nnrrmlpf-p  r>pll«    prm  7)>  Schultz*  cube,  made  of  glass  1  c.c.  in  depth,  in- 

ana  Complete  CeilS,  COU-          traduced  into  the  chamber. 

sisting    of    naked    granular 

protoplasm,  with  one  or  more  nuclei,  which  are  not  easy  to  dis- 


FIG.  40. — Different  kinds  of  human  leucocytes  examined  either  in  the  fresh  state,  or  after  fixation 
with  various  reagents,  magnification  about  1000  diameters  (partly  from  Kanthack  and  Hardy). 
a,  a,',  b,  Fresh  leucocytes  of  three  different  sizes,  in  the  resting  state  ;  c,  the  same  in  amoeboid 
state ;  d,  polynuclear  acidophile  leucocytes  with  )arge  (d')  and  line  (d")  granulation  ;  e,  e',  c", 
hyaline  leucocytes,  destitute  of  grannies ;  /,  lymphocytes ;  g,  leucocytes  with  basophile 
granulation. 

tinguish  in  the  fresh  state,  but  may  become  very  conspicuous  on 
adding  a  drop  of  acetic  acid  to  the  microscopic  preparation. 
VOL.  I  I 


114  PHYSIOLOGY  CHAP. 

The  varying  character  of  the  protoplasm  and  nucleus  make  it 
possible  to  distinguish  several  kinds  of  leucocytes.  From  their 
size,  and  probably  from  their  various  grades  of  development^ 
Schultze  recognised  three  varieties ;  the  smallest  attain  at  most  a 
diameter  of  5  //,  and  possess  a  large  nucleus,  the  medium  have  an 
average  of  7  /*,  the  largest  of  9  /x ;  the  latter  are  often  multinuclear 
and  of  irregular  external  shape.  In  the  foetus  of  less  than  four 
months  there  are  still  larger  ones  which  may  reach  15-19  /*  (Fig.  40). 

According  to  a  more  rational  classification  proposed  by  Ehrlich 
and  Engel,  leucocytes  are  divided  into  two  classes:  those  with 
and  those  without  granules.  The  leucocytes  with  granules  are 
distinguished  as  mononuclear  and  polynuclear,  and  by  their 
staining  affinity,  as  acidophile,  neutrophile,  and  basophile. 

Mononuclear  leucocytes  with  granules  are  extremely  rare,  or 
entirely  absent,  in  normal  circulating  blood;  according  to  many 
authors  they  represent  the  transition  forms  to  polynuclear 
correspondents.  Polynuclear  neutrophile  leucocytes  constitute 
the  greater  part  of  the  white  corpuscles  (from  -3-  to  f)«-.they  have 
a  diameter  of  9-10  //,  exhibit  lively  amoeboid  movements,  and 
perform  the  function  of  phagocytosis.  Polynuclear  leucocytes 
with  fine  or  coarse  acidophile  granulations  are  very  scarce 
(from  2  per  cent  to  4  per  cent).  Still  rarer  in  the  circulating 
blood  are  those  with  basophile  granulations  (0*5  per  cent) ;  they 
are  found  almost  exclusively  in  the  tissues  of  the  haematopoietic 
organs. 

The  non-granular  leucocytes  are  distinguished  as  lymphocytes, 
large  lymphocytes,  large  mononuclear  cells  and  inflammatory 
forms.  The  lymphocytes  are  the  size  of  normal  erythrocytes,  with 
a  reticular  nucleus  which  occupies  nearly  the  whole  cell.  They 
represent  about  |  the  total  number  of  white  corpuscles;  their 
number  varies  not  merely  in  certain  physiological  conditions,  as 
for  instance  in  digestion,  but  also  in  pathological  states. 

The  large  lymphocytes,  large  mononuclear  cells,  and  in- 
flammatory forms  have  precisely  similar  characters  to  the  pre- 
ceding ;  they  are  differentiated  by  the  volume  of  their  protoplasm. 
These  cells  are  comparatively  rare  in  normal  blood,  and  are  more 
interesting  to  the  pathologist  than  to  the  physiologist. 

Many  clinical,  anatomical,  and  experimental  researches  have 
been  directed  to  the  object  of  establishing  the  relations  existing  in 
last  resort  between  the  lymphocytes  and  the  granular  leucocytes 
with  polymorphous  nuclei,  as  well  as  the  general  relations 
between  the  various  white  morphological  elements  of  the  blood. 
Here  we  must  only  say  that  while  Ehrlich's  theory  admits  a  sharp 
distinction  between  the  cells  derived  from  the  lymphatic  system 
and  those  derived  from  bone-marrow,  there  is  another  opposing 
theory,  according  to  which  the  lymphocytes  are  the  young  cells 
which  give  rise  to  all  other  elements  of  the  blood  (Ouskoff). 


iv  THE  BLOOD:   FOKMED  CONSTITUENTS          115 

Notwithstanding  these  different  theories  and  conflicting  argu- 
ments, Ehrlich's  view  is  that  generally  supported. 

In  the  circulating  blood  the  white  corpuscles  are  almost  always 
round,  and  since  their  specific  gravity  is  somewhat  lower  than 
that  of  the  erythrocytes,  they  leave  the  more  rapid  axial  current 
of  the  vessels  and  follow  the  slower  peripheral  stream,  keeping  in 
perpetual  contact  with  the  internal  walls  of  the  vessels  and  con- 
stantly rotating  along  them  (cycloid  movement).  When  observed 
in  an  isolated  drop  of  blood,  the  object-carrier  of  the  microscope 
being  warmed  to  35-40°  C.,  it  is  easy  to  recognise  their  mobility,, 
which  exactly  resembles  that  of  the  Amoeba,  so  that  Lierberktihn 
(1854),  who  was  the  first  to  study  and  describe  them  exactly, 
regarded  leucocytes  as  peculiar  parasitic  amoebae.  It  is  more 
interesting  to  watch  the  amoeboid  movements  of  the  leucocytes 
within  the  blood -stream.  Cohnheim  (1869)  was  the  first  to 
demonstrate  the  fact  that  leucocytes,  by  their  amoeboid  properties, 
are  capable  of  perforating  the  internal  walls  of  the  smallest  veins 
by  a  pseudopodium  and  of  passing  their  whole  body,  little  by  little, 
through  the  temporary  wound  thus  formed,  as  through  a  mesh,, 
emigrating  in  this  way  from  the  blood  torrent  into  the  interstices 
or  plasma  canals  of  the  tissues.  This  emigration  may  become 
tumultuous  in  tissues  that  have  suffered  inflammatory  irritation 
(natural  or  experimental).  The  pathological  doctrine  of  suppura- 
tion and  formation  of  abscesses  is  definitely  co-ordinated  with 
this  fact.  The  more  recent  researches  of  Thomas,  Eecklinghausen 
and  others  have  demonstrated  that  corpuscular  diapedesis  must  be 
regarded  not  as  a  passive  extravasation,  but  as  an  active  emigra- 
tion due  (as  was  Cohnheim's  original  idea)  to  the  amoeboid 
mobility  of  the  leucocytes. 

The  discovery  of  Phagocytosis,  founded  more  particularly  on 
the  elegant  researches  of  Metschnikoff  (1892),  added  new  and 
interesting  arguments  for  the  close  approximation  between 
leucocytes  and  amoebae.  Even  when  removed  from  the  blood,  and 
observed  with  the  microscope,  leucocytes,  like  amoebae,  are  seen  to- 
be  capable  of  ingesting  many  foreign  bodies,  by  surrounding  them 
with  protoplasm,  whether  these  are  inorganic  particles  (such  as 
carmine  granules  and  other  colouring  matters),  fat  drops,  dead  cells 
or  fragments  of  cells,  or  living  cells  and  microbes  '(e.g.  erythrocytes- 
and  bacteria)  of  various  pathogenic  or  non-pathogenic  species. 

Leucocytes,  like  amoebae,  are  capable  of  digesting  dead  bodies,, 
and  of  chemically  killing  and  dissolving  the  living  cells  and 
microbes  which  they  have  ingested.  The  red  corpuscles  thus- 
dissolve  slowly  in  the  interior  of  the  phagocytes  (large  leucocytes),, 
leaving  a  residue  of  pigment.  They  exercise  a  similar  dissolving 
action  upon  pus  granules  (dead  or  dying  leucocytes),  on  the  fibrin 
of  inflammatory  exudates,  and  on  muscle  fibres  in  cases  of  acute 
atrophy  of  the  muscular  tissue.  Lastly,  the  phenomenon  of  the 

VOL.  I  i  a 


116  PHYSIOLOGY  CHAP. 

digestion  of  the  microbes  englobed  by  leucocytes  (anthrax  bacilli, 
spirilli  of  recurrent  fever,  vibrios  of  septicaemia,  streptococci  of 
erysipelas)  have  been  directly  observed  in  various  phases.  These 
facts  are  much  in  favour  of  Metchnikoff  s  view  that  the  protoplasm 
of  leucocytes  contains  enzymes  which  are  more  active  than  the 
secretions  of  the  digestive  glands  of  higher  animals  (pepsin  and 
trypsin),  since  the  latter  fail  to  kill  the  same  microbes. 

According  to  Leber,  Massart,  Bordet  and  other  observers,  the 
migratory  and  phagocytic  faculties  of  the  white  corpuscles  are 
phenomena  of  chemotaxis  (i.e.  the  property  of  being  attracted  or 
repelled  by  certain  chemical  compounds,  even  at  a  distance).  It 
is  a  fact  that  leucocytes  do  not  devour  all  the  species  of  microbes 
which  they  encounter  in  their  wanderings,  but  are  capable  (at  least 
up  to  a  certain  point)  of  selecting  the  prey  on  which  they  feed. 
In  the  body  the  physiological  function  of  the  leucocytes  depends 
essentially,  as  we  shall  see  below,  upon  their  phagocytic  capacity. 

The  number  of  leucocytes  varies  conspicuously,  even  under 
physiological  conditions.  This  may— partially  at  leas-t — be  ex- 
plained by  the  fact  that  they  are  continually  (in  different  degrees, 
according  to  the  functional  state  of  the  viscera)  emigrating  from 
the  lymphatic  system,  in  which  they  originate,  to  the  vascular 
system,  and  thence  again  by  diapedesis  into  the  lymphatic  system. 

The  method  for  counting  leucocytes  is  fundamentally  the 
same  as  for  the  enumeration  of  erythrocytes.  In  normal  blood 
their  number  is  much  lower  than  that  of  the  erythrocytes. 
According  to  Grancher,  there  are  in  healthy  young  people  of 
twenty  to  thirty,  3000  to  9000  leucocytes  in  1  c.mm.  at  different 
hours  of  the  day.  The  ordinary  ratio  between  these  and  the 
•erythrocytes  would  be  from  1:1200  to  1:1500,  but  it  may  increase 
to  a  maximum  of  1:900.  According  to  Malassez,  on  the  other 
hand,  there  are  4000-7000  leucocytes  per  c.mm.  in  healthy  persons ; 
and  the  ratio  with  the  erythrocytes  is  from  1:1250  to  1:1650. 
It  must  always  be  remembered  that  the  number  of  leucocytes 
varies  according  to  the  vascular  region  from  which  the  blood  is 
drawn,  and  with  age,  season,  state  of  nutrition,  in  menstruation, 
pregnancy,  etc.  Disease  has  the  greatest  influence  on  the  number 
of  leucocytes;  during  suppuration,  but  especially  in  certain 
morbid  states  (leucaemia),  their  numbers  may  be  enormously 
increased,  and  their  ratio  with  the  red  corpuscles  may  rise  to  1:15 
or  even  higher.  On  the  other  hand,  it  should  be  noted  that  the 
opposite  occurs  during  the  first  week  of  an  absolute  fast,  when 
there  is  marked  and  progressive  diminution  of  the  leucocytes 
(Luciani). 

It  has  not  hitherto  been  found  possible  to  examine  the 
chemical  composition  of  the  leucocytes  of  the  blood,  owing  to  the 
difficulty  of  separating  them  from  the  plasma  without  admixture 
of  other  elements.  The  first  observations  on  this  subject  were 


iv  THE  BLOOD:   FOEMED  CONSTITUENTS          117 

based  on  the  researches,  first  of  Miescher  and  subsequently  of 
Hoppe  -  Seyler,  on  the. composition  of  pus.  Pus  cells,  however, 
are  essentially  composed  of  extravasated  leucocytes  which  have 
lost  their  vitality  in  great  measure,  or  are  on  the  way  to  dissolution. 
They  cannot,  therefore,  have  the  same  chemical  composition  as 
young  and  normal  leucocytes. 

Lilienfeld  has  recently  studied  the  chemical  composition  of  the 
leucocytes  of  the  lymph  (lymphocytes) — which  are  richly  distri- 
buted in  the  reticulum  of  the  lymphatic  glands — with  interesting 
'results. 

When  a  considerable  quantity  of  lymph  nodules  previously 
freed  from  fat  and  blood-vessels  is  put  under  pressure,  a  turbid 
juice  is  yielded  containing  many  well-preserved  leucocytes,  which 
can  be  separated  from  the  liquid  by  centrifuging.  These  readily 
dissolve  in  water,  and  it  is  possible  with  magnesium  sulphate  to 
obtain  two  globulins  from  the  filtrate  of  the  watery  extract,  one  of 
which  coagulates  at  73-75°  C.,  the  other,  on  the  contrary,  at  48°  C. 
If  dilute  acetic  acid  be  added  to  the  filtrate  of  the  watery  extract,  a 
phosphorus-containing  substance  belonging  to  the  group  of  nucleo- 
proteins,  which  Lilienfeld  terms  nucleo-histone,  is  precipitated,  and 
this  is  the  principal  constituent  of  the  nucleus,  not  only  in 
leucocytes,  but  in  other  cells  also. 

Nucleo-histone  (which  can  be  obtained  pure,  in  the  form  of  a 
white  powder,  soluble  in  water)  breaks  up,  on  treatment  with 
baryta,  or  with  dilute  hydrochloric  acid,  or  boiling  water,  into  its 
two  component  groups:  a  nuclein,  which  Lilienfeld  calls  leuco- 
nuclein,  and  an  albuinose,  which,  as  we  have  seen,  was  in  the  first 
instance  extracted  by  Kossel  from  the  nuclei  of  birds'  erythrocy  tes, 
and  which  he  called  histone. 

On  making  an  alcoholic  extract  from  the  mass  of  leucocytes 
(obtained  as  above)  it  is  found  to  contain  protagon,  lecithin, 
cholesterin,  inosit,  and  potassium  phosphate.  Fat  is  exhibited  by 
an  ethereal  extract. 

Besides  these  substances,  leucocytes  contain  a  small,  constant 
amount  of  glycogen  (Hoppe-Seyler). 

According  to  Lilienfeld,  the  quantitative  per  cent  composition 
of  leucocytes  is  as  follows  : — 

Protein  substances     .         .         .         .         .         .  1'76 

Leuconuclein 6878 

Histone 8-67 

Lecithin     .........  7*51 

Fat 4-02 

Cholesteriii         ........  4*40 

Glycogen    .         .         . 0'80 

Nuclein  bases  (weighed  as  silver  compounds)    .         .  15*17 

IX.  The  Blood-Platelets,  which  Bizzozero  (1880)  regarded  as 
the   third   formed   element   of  the   blood,   had   been   previously 
VOL.  i  I  & 


118  PHYSIOLOGY  CHAP. 

described  by  Hayem  under  the  name  of  haematoblasts,  because 
they  were  erroneously  considered  to  be  the  precursors,  or  early 
stages  of  development,  of  the  erythrocytes  (Fig.  41).     They  are  in,- 
the  form  of  circular  flat  discs  and  consist  of  a  finely  granulated, ' 
highly  refrangible  substance,  colourless  (hence  entirely  destitute  of 
haemoglobin),  and  staining  fairly  intensely  with  aniline  dyes.    They 
are  two  to  three  times  smaller  than  the  erythrocytes  (2-3  /* ;  see 

Fig.  41).  Their  number  varies 
% '"  from  200,000  to  500,000  per 
&  c.nmi.  The  numerical  relation 

of  the  leucocytes  to  the  plate- 
:     lets   is   about    1  : 40,   and   of 
the  platelets  to  the  erythro- 

Fio.  41.— Blood-platelets  viewed   from  the  surface    CyteS  about  1:25.       Their  Slll'- 
and  laterally :  highly  magnified.     In  the  centre  is     n          •      r,  •    i  i  •  j 

an  eiythrocyte  for  comparison  of  size.  lace  IS  highly    VISCOUS,  and    111 

stagnant  blood  they  agglutin- 
ate, forming  granulated  heaps  which  readily  break  up  and  dissolve 
in  the  plasma. 

Lowit  is  of  opinion  that  the  platelets  are  formed  by  disintegra- 
tion of  the  leucocytes,  and  are  not  pre-existent  in  the  blood  before 
it  is  extracted  from  the  vessels.     Bizzozero,  however,  proved  that 
they  can  easily  be  seen  in  the  mesenteric  vessels  of  guinea-pigs, 
and  in  the  wings  of  bats,  on  retarding  the  circulation.     Osier,  in 
investigating  the  mesentery  of  the  mouse  (Fig.  42),  confirmed  this 
observation.    But  the  fact  that  they  are  found  in  living,  circulating 
blood  does  not  seem  a  sufficient   argument   for  regarding   them 
as  distinct  morphological  and  physio- 
logical individuals.     Lilienfeld's   later          Jnu-^frj     mr  '._* 
researches   proved    that   the    platelets          ^^&  Q^\°'*  !»$ 
contain  nuclein  in  the  form  of  nucleo-  ^^l^0^0^! 

albumin,  the  micro-chemical  reactions         ..-LJl^  ° s ""  °  *°  f~ 
of  which  are  similar  to  those  of  the 

nuclei  Of  the  leUCOCyteS.        It  Seems  not    Fi««.     4-1.  —  Erythrocytes    and    blood- 

improbable  that  they  are  derived  from       ffi±ita<S3£) "" 
the   latter,  owing  to  disintegration  of 

,  cellular  protoplasm.  Besides  blood-platelets,  the  older  observers 
detected  granules  and  irregular  protoplasmic  fragments  of  various 
dimensions  (and  quite  distinct  from  the  fat  drops  that  dissolve 
in  ether)  in  the  blood,  which  evidently  originate  in  the  disintegra- 
tion of  the  protoplasm  of  the  lymphatic  cells  or  leucocytes;  on 
this  they  founded  the  hypothesis  that  the  platelets  too  are  derived 
from  the  disintegration  of  leucocytes. 

In  accordance  with  this  theory,  Fano  has  demonstrated  that 
there  are  scarcely  any  platelets  in  dog's  lymph.  Probably  this  is 
due  to  the  fact  that  the  younger  lymphatic  cells  predominate  in 
lymph,  and  that  their  protoplasm  disintegrates  less  readily.  It 
should  also  be  added  that  blood-platelets  of  characteristic  form 


iv  THE  BLOOD :   FOBMED  CONSTITUENTS          119 

do  not  exist  in  blood  that  has  been  whipped  and  defibrinated,  and 
that  they  disappear  from  the  blood  of  dogs  that  have  been 
repeatedly  bled,  with  subsequent  infusions  of  the  same  blood  after 
it  has  been  defibrinated.  In  such  animals  nothing  otherwise 
abnormal  can  be  detected,  and  the  blood -platelets  gradually 
reappear,  and  are  present  in  their  usual  number  after  a  few  days 
(Gad).  On  the  theory  that  the  platelets  originate  in  the 
decomposition  of  leucocytes,  the  explanation  of  these  facts  may  be 
that  the  young  leucocytes,  supplied  to  the  blood  by  the  lymphatic 
system,  require  a  certain  time  to  develop,  become  adult,  grow  old, 
and  disintegrate,  when  their  nuclei  give  rise  to  the  formation  of 
new  platelets. 

On  the  other  hand,  not  a  few  of  the  recent  workers  in  this 
field  incline  from  many  standpoints  to  the  view  that  the  platelets 
originate  from  the  red  corpuscles. 

Kb'ppe,  Hirschfeld,  and  Pappenheim  observed  that  a  certain 
number  of  erythrocytes  are  spherical  in  form,  without  depressions, 
within  which  are  masses  that  stain  pink  with  tri-acid,  and  faint 
turquoise  with  methylene  blue,  and  which  when  isolated  differ  in 
no  respect  from  blood  -  pla telets  ;  while  blood  -  platelets  can  often 
be  distinguished  among  the  erythrocytes.  Other  observers  hold 
that  the  ery throcy te  consists  of  two  parts — a  central,  and  a  peri- . 
pheral  stratum.  The  peripheral  layer  contains  the  haemoglobin 
(Foa) :  beneath  this  lies  the  true  protoplasm. 

It  must  also  be  remembered  that  according  to  Engel,  every 
non- nucleated  blood -corpuscle  has  at  one  time  or  other  been 
one  of  those  nucleated  corpuscles  of  which  the  mantle  contains 
haemoglobin  and  is  aurantiophile,  its  chroniatin  consisting  of 
nuclein,  and  its  achromatic  acidophile  substance  containing 
protein.  When,  under  normal  conditions,  the  nuclei  of  the  red 
nucleated  corpuscles  apparently  disappear  in  kariolysis,  the  nuclei 
lose  their  shape,  but  the  chemical  substances  of  which  they  are 
composed  persist  under  other  forms.  One  form  of  these  nuclear 
rests  is  the  basophile  granulation  of  the  erythrocytes  (see  below) ; 
the  other,  more  common,  form  is  represented  by  the  almost 
amorphous  blood  platelets.  On  this  theory  it  may  be  said  that 
every  red  corpuscle  of  the  depressed  form  has  already  lost  its 
platelets,  while  erythrocytes  from  which  the  platelets  are  on  the 
point  of  issuing,  or  in  which  they  are  still  confined  within  the 
corpuscle,  are  the  more  nearly  spherical. 

This  mode  of  origin  of  the  blood-platelets  would  account  for 
the  appearance  they  sometimes  present  of  escaping,  even  where 
detachment  is  not  complete.  The-  body  thus  detached  may,  even 
if  rarely,  resemble  a  nucleus  surrounded  by  protoplasm. 

Foa  has  recently  (on  repeating  with  modern  methods  of  fixing 
and  staining  the  experiments  he  made  in  1889,  in  collaboration 
with  Carbone)  confirmed  the  existence  of  platelets  in  the  spleen 

VOL.  i  I  c 


120  PHYSIOLOGY  CHAP. 

which  are  identical  with  those  circulating  in  the  blood ;  these,  he 
maintains,  are  not  simply  deposited  there,  but  originate  in  situ. 
According  to  Foa  the  platelets  are  autonomous  elements,  and/v 
since  they  are  composed  of  protoplasm  and  nuclear  substance,  are 
real  cells  sui  generis,  capable  of  multiplying  by  direct  division  in 
the  circulating  blood. 

In  view  of  the  importance  assigned  to  the  platelets  in  respect 
of  blood  coagulation,  we  shall  return  to  them  after  considering  the" 
chemical  constitution  of  blood  plasma. 

The  microscopic  examination  of  the  blood  can  be  made  with  fresh  or  fixed 
preparations.  It  is  essential  to  use  slides  and  cover-glasses  that  have  been 
scrupulously  cleaned  (first  in  alcohol  containing  HC1,  and  then  in  ordinary 
alcohol)  and  well  dried  with  a  linen  cloth.  The  blood  required  is  obtained 
by  pricking  the  ball  of  the  finger  or  lobe  of  the  ear  with  a  needle  (better,  a 
lancet),  so  that  the  blood  wells  out  in  drops  without  employing  compression. 
In  order  to  examine  fresh  preparations  microscopically,  it  is  only  necessary  to 
take  up  a  drop  of  blood  on  the  cover-glass  and  lay  this  on  the  slide  with  the 
drop  downwards.  If  the  glasses  are  clean,  the  blood  spreads  uniformly  between 
them,  and  the  preparation  only  needs  a  gentle  tap  on  the  coYer-glass  to 
distribute  the  morphological  elements  in  an  even  layer  and  make  it  ready 
for  observation. 

In  order  to  keep  the  formed  constituents  of  the  blood  alive  for  prolonged 
observation,  a  drop  of  blood  must  be  gently  compressed  between  two  cover- 
glasses,  which  are  then  separated  by  drawing  one  across  the  other.  One  of 
these  films  is  laid  over  the  central  depression  of  a  special  slide,  such  as  is  used 
for  the  observation  of  bacteria  in  hanging  drops.  The  margin  of  this  de- 
pression is  previously  filled  with  vaseline  to  prevent  the  intrusion  of  air,  which 
would  cause  the  preparation  to  dry  up — making  a  minute  moist  chamber. 
The  preparation  is  then  placed  on  Schultze's  warm  carrier  and  kept  at  the 
required  temperature. 

The  fixing  of  the  blood  for  microscopic  study  is  performed  in  two  different 
ways,  by  the  wet  or  the  dry  method.  To  fix  it  by  the  wet  method  the  blood 
is  collected  in  a  watch-glass  and  the  various  fixing  solutions  added.  Such  are 
solutions  of  osmic  acid,  corrosive  sublimate,  palladium  chloride,  Kleinenberg's 
picro-sulphuric  acid,  Flemming's  osmic  -  chrom  -  acetic  mixture,  etc.  When 
completely  fixed,  the  solution  is  removed,  and  the  preparation  can  be  examined 
immediately  or  after  staining.  Fixing  by  the  dry  method  is  effected  by 
warming  the  film  preparation.  It  must  be  dried  in  the  air,  and  then  passed 
6-10  times  through  the  flame  of  a  spirit  lamp,  care  being  taken  not  to  scorch 
it ;  or  it  may  be  laid  for  about  an  hour  on  a  copper  plate,  warmed  to  120°. 
Fixation  is  also  effected  by  placing  the  air-dried  blood  film  for  an  hour  in  a 
mixture  of  equal  parts  of  absolute  alcohol  and  ether. 

Excellent  results  are  obtained  by  warming,  and  then  dipping  into  alcohol 
and  ether. 

Staining  is  necessary  in  studying  the  detailed  structure  of  the  formed 
elements  of  the  blood.  To  stain  fresh  preparations,  weak  solutions  of  iodine, 
methyl-violet,  methylene-blue,  eosin,  etc.,  must  be  used.  For  staining  dry 
preparations,  countless  methods  are  described  in  special  text-books,  but  we 
must  here  confine  ourselves  to  the  most  ordinary,  which  are  also  the  most 
practical  for  the  doctor.  The  film-preparations  are  passed  6-10  times  through 
the  flame  of  a  lamp,  and  then  placed  for  about  half-an-hour  in  equal  parts  of 
absolute  alcohol  and  ether.  They  are  then  dried  again  in  the  air,  and  stained 
in  a  watch-glass  with  Ehrlich's  acid  haematoxylin  (haematoxylin  2  grins., 
absolute  alcohol  60  grms.).  To  this  first  solution  is  added  the  following  mixture, 
which  has  previously  been  saturated  with  alum  :  glycerin  60  grms.,  distilled 


iv  THE  BLOOD:   FORMED  CONSTITUENTS          121 

water  60  grms.,  acetic  acid  3  grms.  In  5-10  minutes  the  cover-glasses  are  taken 
out  of  the  haematoxylin,  washed  in  water,  and  stained  for  the  second  time  by 
dipping  them  for  a  few  moments  into  a  1  per  cent  solution  of  eosin.  They 
are  then  washed  again  in  distilled  water,  wiped  at  the  edges  with  filter-paper, 
dried  over  the; flame,  and  mounted  on  the  slide  with  a  drop  of  Canada  balsam 
dissolved  in  xyloL 

The  nuclei  and  blood-platelets  stain  blue  with  the  haematoxylin,  .the 
protoplasm  pink  with  the  eosin. 

A  copious  literature  has  recently  sprung  up  in  regard  to 
flsmotic  phenomena,  and  the  resistance  of  the  erythrocytes  to 
yielding  their  haemoglobin,  when  brought  into  salt  solutions  of 
different  concentrations.  Since,  however,  this  subject  is  intimately 
•connected  with  the  physico-chemical  structure  of  the  blood 
plasma,  we  shall  consider  it  in  the  next  chapter. 

The  important  question  of  the  origin,  formation,  and 
destruction  of  Erythrocytes  and  Leucocytes  will  be  discussed  in 
treating  of  the  function  of  the  haematopoietic  and  haematolytic 
organs. 

BIBLIOGRAPHY 

WELCKER.     Zeitschr.  f.  rat.  Med.,  1858. 

PREYER.     Die  Blutkrystalle.     Jena,  1871. 

A.  ROLLETT.     Hermann's  Handbuch  d.  Physiol.,  4,  1880. 

•C.  BIZZOZERO.     Arch.  It.  Biol.,  1882,  1883. 

HAYEM.     Arch,  de  pliysiol.,  1883.     Gaz.  med.,  1883. 

HEDIN.     Strass.  Arch.  f.  Physiol.,  1890. 

E.  A.  SCHAFER  and  A.  GAMGEE.     Schafer's  Text-Book  of  Physiology,  i.  1898. 
H.  F.  HAMBURGER.     Osmotischer  Druck  u.  lonenlehre.     Wiesbaden,  1901-5. 
R.  HOBER.     Phys.  Chemie  der  Zelle  u.  der  Gewebe,  2nd  ed.     Leipzig,  1906. 

F.  WEIDENREICH.     Die  roten  Blutkbrperchen-Ergebnisse.     Merkel  and  Bonnet, 

1903-4. 

•GRAWITZ.     Klin.  Path,  des  Blutes,  1902. 
ENGEL.     Leitfaden  z.  klin.  Unters.  des  Blutes,  1902. 
FOA.     Arch.  d.  scienze  med.     Turin,  1906. 

Recent  English  Literature  : — 

W.  MYERS.     The  Causes  of  the  Shape  of  Non-nucleated  Red  Blood  Corpuscles. 

Journ.  of  Anat.,  xxxiv.  3,  p.  351. 
A.  GAMGEE.     On  the  Behaviour  of  Oxy haemoglobin,  etc.,  etc.,  in  the  Magnetic 

Field.     Proc.  Roy.  Soc.,  Ixviii.  450,  p.  503. 
J.    HALDANE.      The    Colorimetric    Determination   of   Haemoglobin.      Journ.    of 

Physiol.,  1900-1,  xxvi.  497. 

G.  N.  STEWART.     The  Conditions  that  underlie  the  Peculiarities  in  the  Behaviour 

of  the  Coloured  Blood  Corpuscles  to  certain  Substances.     Journ.  of  Physiol., 

1900-1,  xxvi.  470. 
5.  PESKIND.     Notes  on  the  Action  of  Acids  and  Acid  Salts  on  Blood  Corpuscles 

and  some  other  Cells.     Amer.  Journ.  of  Physiol.,  1903,  viii.  99  and  404. 
O.    N.    STEWART.      The   Behaviour  of  Nucleated   Blood  Corpuscles    to    certain 

Haemolytic  Agents.     Amer.  Journ.  of  Physiol.,  1903,  viii.  103. 
•G.  T.  .KEMP.     Relation  of  Blood  Plates  to  the  Increase  in  the  Number  of  Red 

Corpuscles  at   High  Altitudes.      Proc.    of  the   Amer.    Physiol.  Soc.  (Amer. 

Journ.  of  Physiol.),  1902,  vi.  p.  xi. 
•G.  T.   KEMP  and   0.  0.    STANLEY.     Some-  New   Observations  on   Blood   Plates. 

Proc.  of  the  Amer.  Physiol.  Soc.  (Amer.  Journ.  of  Physiol.),  1902,  vi.  p.  xi. 
€.  C.  GUTHRIE.     The  Laking  of  Dried  Red  Blood  Corpuscles.     Amer.  Journ.  of 

Physiol.,  1903,  viii.  441. 
•G.  N.  STEWART.     The  Influence  of  Cold  on  the  Action  of  some  Haemolytic  Agents. 

Amer.  Journ.  of  Physiol.,  1903,  ix.  72. 


122  PHYSIOLOGY  £HAP.  iv 

E.   T.    REICHEIIT.      Quick  Methods   for  Crystallising   Oxyhaemoglobin.      Amer. 

Journ.  of  rhysiol.,  1903,  ix.  97. 
P.    B.    HAWK.      On   the    Morphological   Changes   in    the    Blood   after   Muscular^ 

Exercise.     Amer.  Journ.  of  Physiol.,  1904,  x.  384. 
P.  P.  LATDLAW.      Some  Observations  on  Blood  Pigments.     Journ.   of  Physiol., 

1904,  xxxi.  464. 

C.  E.  HAM  and  H.  BALEAN.    The  Effects  of  Acids  upon  Blood.    Journ.  of  Physiol., 

1905,  xxxii.  312. 

S.  PESKIND.     Ether-laking  :  A  Contribution  to  the  Study  of  Laking  Agents  that 

Dissolve  Lecithin  and  Cholesterin.     Amer.  Journ.  of  Physiol.,  1905,  xii.  184. 
C.   G.   DOUGLAS.     A  Method  for  the   Determination  of  the  Volume  of  Blood  in 

Animals.     Journ.  of  Physiol.,  1905-6,  xxxiii.  493. 
E.  W.  REID.   Osmotic  Pressure  of  Solutions  of  Haemoglobin.     Journ.  of  Physiol., 

1905-6,  xxxiii.  12. 
T.  W.  CLARKE  and  W.  H.  HUHTLEY.     On  Stilph-haemoglobin.     Journ.  of  Physiol., 

1907-8,  xxxvi.  62. 
H.   C.  Ross.     On   the    Death  of  Leucocytes.     Journ.    of  Physiol.,  1908,    xxxvii. 

327. 
H.    C.    Ross.     On  the  Yacuolation  of  Leucocytes  and  the  Liquefaction  of  their 

Cytoplasm.     Journ.  of  Physiol.,  1908,  xxxvii.  333. 


CHAPTER   V 

THE   BLOOD :    PLASMA 

CONTENTS.  —  1.  Different  methods  for  separation  of  blood  plasma  from 
corpuscles.  2.  Histogenic  substances  or  proteins  of  plasma  :  iibrinogen,  serum 
globulin,  serum  albumin,  sero-mucoid.  3.  Nitrogenous  histolytic  products  of 
plasma.  4.  Fatty  substances.  Carbohydrates  and  their  derivatives.  5.  Inorganic 
substances.  Blood  gases.  6.  Theory  of  Coagulation :  (a)  conditions  of  blood 
coagulation  ;  (b)  disintegration  of  corpuscles  as  cause  of  coagulation ;  (c) 
fibrinogen  as  fibrin  generator  ;  (d)  analogies  between  blood  coagulation  and 
curdling  of  milk  ;  (<•)  importance  of  time  in  coagulation  ;  (/)  thrombin  and 
nucleins  as  coagulating  substances ;  (<j]  histone  and  cytoglobulin  as  anti- 
coagulating  substances.  7.  Osmotic  pressure,  molecular  concentration,  electrical 
conductivity  and  viscosity  of  blood  and  serum.  8.  Functions  of  the  blood  :  (a] 
effects  of  bleeding  ;  (b)  effects  of  transfusion  of  homo-  and  heterogeneous  blood  ; 
(c)  bactericidal  and  immunising  properties  of  blood  and  serum.  Bibliography. 

I.  THE  property  by  which  the  blood  coagulates  spontaneously  a 
few  moments  after  it  has  been  drawn  from  the  veins,  and  the 
instability  of  the  corpuscles,  which  renders  them  liable  to  injury 
from  the  slightest  causes,  owing  to  modification  of  their  osmotic 
and  secretory  properties,  make  it  difficult  and  almost  impossible 
to  separate  the  plasma  from  the  total  mass  of  corpuscles,  or  formed 
elements,  in  the  identical  amount  and  composition  in  which  it 
circulates  in  the  vessels. 

To  effect  this  as  perfectly  as  possible,  horse's  blood  must  be 
employed,  since  this,  as  has  been  said,  coagulates  slowly,  and  gives 
time  for  the  red  corpuscles  (which  have  a  higher  specific  gravity) 
to  separate  partially  from  the  plasma  and  sink  towards  the 
bottom  of  the  vessel.  If  the  blood  streaming  from  the  veins  is 
cooled  to  about  0°  C.  by  receiving  it  in  a  tall  narrow  cylindrical 
vessel,  surrounded  with  ice,  coagulation  can  be  retarded  so  long 
that  after  about  an  hour  the  transparent  plasma,  free  from 
erythrocytes,  and  containing  only  a  small  admixture  of  leucocytes, 
floats  on  the  corpuscles,  and  can  be  removed  with  a  previously 
cooled  pipette  (Briicke).  It  is,  however,  impossible  by  this 
method,  even  with  all  the  precautions  suggested  by  experience, 
to  avoid  a  certain  diffusion  of  haemoglobin  from  the  corpuscles  to 
the  plasma,  which  then  becomes  more  or  less  tinted  and  shows 
the  characteristic  spectrum  of  oxyhaemoglobin. 

123 


124  PHYSIOLOGY  CHAP. 

If  the  plasma  thus  obtained  by  simple  cooling  of  horse's  blood 
is  warmed  to  the  temperature  of  the  atmosphere,  it  coagulates, 
like  the  blood  in  toto,  arid  an  incoagulable  fluid  separates  outr 
which  is  pure  serum.  If  the  clot  is  squeezed  and  washed  out/ 
the  purest  fibrin  is  obtained.  Serum  is,  therefore,  nothing  but 
plasma  in  which  the  protein  which  gives  rise  to  the  formation 
of  fibrin,  and  was  therefore  termed  fibrinogen,  is  wanting.  Besides 
this  cardinal  difference,  however,  we  shall  see  that  other  secondary 
differences  that  can  be  demonstrated  between  plasma  and  serum 
are  the  result  of  the  coagulation  process. 

Since  the  plasma  of  horse's  blood  can  coagulate,  it  is.  not 
suitable  for  the  examination  of  the  true  proteins  which  it  normally 
contains.  In  order  to  obtain  a  purer  plasma,  as  free  as  possible 
from  corpuscles  and  haemoglobin,  and  at  the  same  time  incoagul- 
able, the  blood  of  a  dog,  into  whose  veins  a  certain  quantity  of 
albumoses  (pro-peptones)  has  been  injected  intravenously  a  few 
minutes  before  the  bleeding  (Schmidt-Miihlheim,  Albertoni,  Fano), 
is  employed.  The  peptonised  blood  obtained  in  this  way  has  lost 
its  faculty  of  spontaneous  coagulation,  so  that  it  is  easy  by 
prolonged  centrifuging  to  separate  the  plasma  completely  from 
the  mass  of  corpuscles.  The  same  effect  is  arrived  at  by  intra- 
venous injection  of  leech-extract  (Haycraft).  Apparently  all 
blood-sucking  animals,  independent  of  their  zoological  position, 
and  merely  in  relation  to  the  nature  of  their  food  and  their  mode 
of  obtaining  it,  possess  substances  in  their  buccal  secretions  which 
impede  coagulation :  such  are  the  leech  (Haycraft),  the  tick 
(Sabbatani),  and  the  mosquito  (Grassi). 

The  plasma  obtained  from  peptonised  blood  is  a  transparent, 
light  yellow  fluid,  absolutely  free  from  haemoglobin ;  under  the 
microscope  it  is  found  to  contain  no  erythrocytes,  and  only  a  few 
leucocytes  and  blood-platelets.  It  does  not  coagulate  spontane- 
ously ;  but  when  diluted  with  an  equal  volume  of  water,  or  when 
a  stream  of  carbonic  acid  gas  is  passed  through  it  for  a  couple  of 
minutes,  it  is  soon  converted  into  a  quivering,  gelatinous  mass, 
from  which  the  serum,  in  which  floats  the  snow-white  cake  of 
pure  fibrin,  separates  out  (Fano). 

Incoagulable  plasma  can  also  be  obtained  by  receiving  the 
blood  that  issues  from  the  veins  in  a  vessel  which  contains  a 
certain  quantity  of  salt  solution,  since,  with  hardly  any  exceptions, 
all  salts  render  the  blood  incoagulable  in  greater  or  less  degree 
owing  to  various  physical  and  chemical  reasons  (Buglia  and 
Gardella).  The  solutions  most  frequently  employed  in  the 
chemical  physiology  of  the  blood  are  sodium  sulphate,  sodium 
chloride,  and  magnesium  sulphate.  Twenty -four  hours  after 
extraction,  or  sooner  if  the  centrifuge  is  used,  the  mass  of  the 
corpuscles  separates  from  the  plasma.  One  inconvenience  of  this 
method  is  that  the  corpuscles  are  deformed,  and  a  considerable 


v  THE  BLOOD:   PLASMA  125 

amount  of  haemoglobin  diffuses  out  and  stains  the  plasma.  The 
separation  of  the  proteins  of  the  blood  in  a  pure  state  was, 
however,  effected  by  A.  Schmidt  and  Hammarsten,  mainly  with 
salted  plasma.  To-day  we  are  acquainted  with  various  less  active 
saline  solutions,  which  when  properly  used  do  not  rupture  the 
erythrocytes,  and  yield  a  perfectly  colourless  plasma ;  among  these 
are  sodium  oxalate  and  metaphosphate. 

Lastly,  it  should  be  noted  that  plasma  can  be  rendered  in- 
coagulable by  adding  sodium  oxalate  to  the  amount  of  0*06 -0*10 
per  cent  to  the  fresh  blood  issuing  from  the  vein.  We  shall 
return  to  these  facts  in  discussing  the  theory  of  coagulation. 

Still  greater  difficulties  arise  when  we  attempt  not  merely  to 
obtain  more  or  less  genuine  plasma,  but  also  to  determine  the 
quantitative  ratio  between  the  normal  mass  of  corpuscles  and  the 
plasma.  The  methods  employed  with  this  object  by  Hoppe-Seyler 
and  Bunge  give  very  different  values,  not  only  for  different 
animals,  but  also  for  different  animals  of  the  same  species.  With- 
out citing  the  results  of  the  various  series  of  observations,  we  may 
say  that  in  man  the  amount  of  plasma  is  slightly  in  excess  of 
that  of  the  corpuscles,  in  the  wet  state :  average,  52  per  cent 
plasma  and  48  per  cent  corpuscles  (Arronet).  In  the  horse,  on 
the  contrary,  the  opposite  result  is  obtained :  average,  47  per  cent 
plasma  and  53  per  cent  corpuscles  (Bunge). 

II.  According  to  recent  analysis,  blood  plasma  contains  on  an 
average  9T8  per  cent  water  and  8'2  per  cent  solid  substances; 
6 '9  per  cent  of  this  consists  of  proteins,  so  that  all  the  other 
constituents  of  plasma  are  reduced  to  I'S.per  cent,  of  which  about 
0*46  per  cent  are  organic  extractives,  0*84  per  cent  inorganic. 

In  all  the  higher  animals  the  proteins  of  blood  plasma  consist 
mainly  of  globulins  (metaglobulin  and  paraglobulin),  and  to  a 
less  degree  of  serum  albumin. 

The  most  important  is  metaglobulin,  commonly  called  fibrino- 
gen,  because  it  gives  rise  during  coagulation  to  fibrin  formation. 
It  is  therefore  entirely  absent  from  serum,  and  to  prepare  it  in  a 
pure  state  salted  plasma  must  be  used,  or  the  morbid  transudations 
of  the  pericardium  (hydropericardial  fluid),  or  the  tunica  vaginalis 
testis  (hydrocele  fluid),  which  always  contain  it.  It  can  be  separated 
out  from  salted  plasma  by  utilising  the  property  which  causes 
fibrinogen  to  precipitate  from  its  solutions  so  soon  as  these 
contain  16  per  cent  of  sodium  chloride,  when  none  of  the  other 
globulins  have  lost  their  solubility,  since  they  are  precipitated 
only  when  their  solutions  are  saturated  with  sodium  chloride. 
To  precipitate  metaglobulin  from,  the  transudates,  it  is  only 
necessary  to  add  sodium  chloride  in  the  solid  form. 

If  a  solution  of  pure  fibrinogen  is  warmed  to  56-60°  C.,  it 
splits  up  into  two  other  globulins,  of  which  we  shall  speak  later, 
and  an  insoluble  coagulum  is  formed. 


126  PHYSIOLOGY  CHAP. 

Paraglobulin  is  also  known  as  serum  globulin,  because  it 
remains  unchanged  in  the  serum  after  spontaneous  blood  coagula- 
tion. It  can  be  readily  separated  in  the  pure  state  by  diluting 
the  serum  with  at  least  ten  volumes  of  water,  and  then  leading  a 
stream  of  carbonic  acid  through  it,  or  by  slightly  acidifying  it  with 
dilute  acetic  acid,  or  by  saturating  it  with  magnesium  sulphate. 

Serum  globulin  dissolved  in  a  10  per  cent  solution  of  common 
salt  coagulates  at  75°  C. 

Serum  albumin  or  serin  is  separated  from  globulins  of  the 
serum  by  salting  the  latter  with  magnesium  sulphate  at  30°  C., 
filtering  it  at  the  same  temperature,  and  adding  to  the  saturated 
filtrate  dilute  acetic  acid,  or  ammonium,  or  sodium  sulphate  to 
saturation.  This  precipitates  the  serum  albumin :  the  precipitate 
is  separated  by  centrifuging,  and  purified  by  dialysis. 

Pure  serum  albumin  dissolved  in  distilled  water  coagulates 
rapidly  at  about  50°  C. ;  but  on  adding  salts  its  heat-coagulability 
is  considerably  lowered.  In  solutions  of  5  per  cent  sodium 
chloride,  coagulation  first  occurs  at  72-75°  C. 

Serum  albumin  is  not  identical  with  ov-albumin,  'as  appears 
from  certain  chemical  properties,  and  more  particularly  from  the 
physiological  characteristic  by  which  the  latter,  when  injected  into 
the  veins,  is  not  retained  in  the  blood,  but  is  at  once  excreted  by 
the  kidneys  and  passes  unchanged  into  the  urine. 

After  Morner  had  isolated  a  protein  of  the  m.ucinoid  group 
from  white  of  egg,  to  which  he  gave  the  name  of  ovo-mucoid, 
Zanetti,  in  Ciamician's  laboratory,  by  a  happy  inspiration  sought 
to  ascertain  whether  the  same  or  some  other  analogous  sub- 
stance were  not  also  contained  in  blood  serum,  which  shows  a 
certain  similarity  to  egg-white  in  its  composition.  His  experiments 
with  ox  serum  were  crowned  with  success.  The  new  substance 
sero-mucoid,  which  he  discovered,  exhibits  physical  and  chemical 
properties  highly  similar  to  those  of  ovo-mucoid. 

The  four  proteins  named  above  are  all  that  have  at  present 
been  definitely  demonstrated  in  blood  plasma.  When  exposed  to 
the  action  of  freely  diluted  acids  or  alkalies,  and  warmed,  they 
turn  into  alkaline  or  acid  albumins,  the  former  being  similar  to 
the  casein  of  milk,  the  latter  to  syntonin.  But  there  is  no 
evidence  for  the  presence  of  these  in  normal  blood  plasma. 

The  quantitative  relation  between  fibrinogen,  serum  globulin, 
and  serum  albumin  is  not  easy  to  determine.  It  appears  probable 
that  the  relative  quantity  of  these  three  proteins  is  very  variable, 
and  that  all  three  function  as  tissue-forming  substances,  the 
albumin  representing  the  true  form,  and  the  two  globulins  two 
different  modifications  produced  by  cell  metabolism.  Miescher 
and  Burckhardt  have  actually  shown  that  the  globulins  of  the 
blood  increase  during  hunger,  while  the  albumin  decreases. 

The   same   facts   and   the   explanation   of  them   have    been 


v  THE  BLOOD:   PLASMA  127 

confirmed  by  many  experiments  carried  out  by  Fano  and  his  pupils 
Ducceschi  and  di  Frassineto,  who  studied  the  blood  in  anaemia,  in 
the  two  sexes,  after  thyroidectomy,  etc. 

The  serum  of  mammalian  blood  contains  a  saccharifying 
ferment,  as  was  pointed  out  by  Magendie,  Cl.  Bernard  and  others. 
Bial  found  that  the  blood  of  man  (obtained  by  bleeding,  or  taken 
from  the  placenta)  also  contained  the  power,  although  in  a  lesser 
degree,  of  converting  starch  paste  into  glucose  and  dextrin,  and  is 
further  capable  of  converting  maltose  into  dextrose.  In  the  new- 
born, in  man  as  in  other  animals,  the  saccharifying  property  is 
very  low,  and  may  be  entirely  absent ;  it  increases  with  age,  and 
with  its  increase  there  is  an  apparent  diminution  in  the  glycogen- 
content  of  the  muscles. 

E.  Cavazzani  found  that  the  quantity  of  haemo-diastase  is  not 
alike  throughout  the  vascular  system ;  the  blood  of  the  portal 
veins  contains  more  than  the  blood  of  the  hepatic  veins,  the 
jugulars,  and  the  carotid  arteries.  This  leads  to  the  conjecture  • 
that  it  originates  in  the  digestive  organs,  and  that  its  presence  in 
the  blood  is  to  a  certain  extent  fortuitous,  and  dependent  on 
digestive  processes. 

According  to  recent  researches,  blood  serum  contains  various 
other  enzymes. 

Claude  Bernard  (in  his  observations  on  the  amount  of  glycogen 
in  normal  dog's  blood)  found  it  necessary  to  test  for  glycogen 
immediately  after  the  blood  had  been  drawTu  from  the  vessels  of  the 
animal,  because  in  a  longer  or  shorter  period,  according  to  the  sur- 
rounding temperature,  it  was  destroyed  by  a  fermentative  process. 

A  similar  disappearance  of  glycogen  (as  also  of  laevulose, 
maltose,  and  galactose)  occurs  on  adding  sugar  artificially  to  the 
blood  in  vitro,  and  it  was  more  particularly  after  the  researches  of 
Lepine  and  Barral  that  this  disappearance  of  sugar  in  the  blood 
was  attributed  to  the  action  of  a  special  glycolytic  enzyme,  which, 
according  to  these  authors,  originated  in  the  white  corpuscles. 
This  glycolysis  is  effected,  according  to  Nasse,  Eohmann  and 
others,  by  an  oxidative  process,  and  more  precisely  by  the  agency 
of  an  oxidising  ferment  (oxidase),  while  according  to  Stoklasa  it  is 
due  to  a  process  analogous  to  alcoholic  fermentation,  to  trie  agency, 
that  is,  of  a  special  zymase. 

In  addition  to  these  two  amylo-  and  glycolytic  enzymes  there 
exists  in  the  serum,  according  to  Hanriot,  a  lipolytic  ferment 
(lipase),  which,  according  to  most  authors,  acts  only  on  inono- 
butyrin,  and  is  incapable  of  splitting  up  olein  and  other  neutral 
fats  (Arthus,  Doyen  and  others).  > 

Along  with  this  restricted   lipolytic   property  of  serum,  the 
blood,  according  to  Connstein  and  Michaelis  and  Weigert,  has  also  C 
a  property  of  transforming  fats  into  certain  soluble  substances,  the 
composition  of  which  is  not  known. 


128  PHYSIOLOGY  CHAP. 

Nor  does  this  complete  the  enumeration  of  all  the  enzymes  in 
blood.  According  to  the  most  recent  researches,  it  further 
contains  oxidases,  catalases,  and  proteolytic  enzymes  (chymosin 
and  trypsin) ;  nor  are  the  corresponding  anti-enzymes  or  anti- 
ferments  lacking;  according  to  Delezenne  there  is  also  an  anti- 
kinase. 

Quantitative  Estimation  of  Fibrinoyen. — The  quantitative  estimation  of  the 
fibrinogen  or  metaglobulin  of  salted  plasma,  which  also  contains  paraglobulin, 
is  based  on  the  different  solubilities  of  these  two  substances  in  salt  solu- 
tions. Hammarsten  (Pflugers  Arch,  xvii.,  xviii.,  xix.)  has  shown  that  para- 
globulin  remains  in  solution  in  water  containing  16-18  per  cent  NaCl,  while 
fibrinogen,  on  the  contrary,  is  completely  precipitated,  and  remains  soluble 
only  at  a  lower  concentration.  If  a  sufficient  quantity  of  saturated  salt 
solution  is  added  to  a  vessel  containing  salted  plasma,  a  flocculent  precipitate 
of  fibrinogen  is  obtained  on  stirring  the  fluid  briskly  with  a  glass  rod.  In 
order  to  purify  this,  it  is  again  dissolved,  after  filtering,  in  an  8  per  cent 
solution  of  NaCl,  and  reprecipitated  with  concentrated  solution  as  before. 
This  operation  is  repeated  three  or  four  times,  and  the  last  precipitate,  which 
is  quite  white,  and  held  in  a  filter  previously  dried  at  115'J  C.,  and  weighed, 
is  placed  in  a  warm  chamber  at  115°  C.  to  coagulate.  The  filter  is  then 
replaced  on  the.  stand  ;  the  coagulated  fibrinogen  is  washed  with  warm  water, 
to  remove  the  salts,  and  then  with  alcohol  and  ether.  The  filter  and  precipi- 
tate are  then  dried  again,  and  weighed  repeatedly  at  long  intervals,  till  a 
constant  weight  is  obtained.  It  is  now  easy  from  the  known  quantity  of 
blood  employed  to  calculate  the  fibrinogen  content  of  100  or  1000  c.c. 

Estimation  of  Fibrin  Ferment. — Carbone's  is  the  only  known  method  of 
estimating  the  fibrin  ferment  contained  in  blood-serum  ;  it  yields  compara- 
tive, not  absolute  results.  This  method  is  based  on  the  fact  that  leech 
extract  acts  in  regard  to  the  ferment  in  a  manner  analogous  to  that  of  anti- 
toxin towards  toxin.  Carbone  mixed  a  constant  quantity  of  fibrinogen 
dissolved  in  0*8  per  cent  NaCl,  in  a  series  of  test-tubes,  with  a  constant 
quantity  of  the  serum  in  which  the  ferment  was  to  be  titrated.  He  then 
added  to  the  different  test-tubes  an  increasing  quantity  of  leech  extract,  and 
eventually  made  the  volume  of  liquid  equal  in  all  by  adding  0'8  per  cent 
NaCl.  After  twenty-four  to  forty-eight  hours  he  examined  the  test-tubes 
and  the  clot,  which  only  formed  where  there  was  little  leech  extract.  He 
estimated  the  quantity  of  ferment  by  the  quantity  of  extract  necessary  to 
neutralise  its  coagulating  action. 

Estimation  of  Paraglobulin. — Magnesium  sulphate  is  added  to  saturation 
to  a  measured  quantity  of  blood  serum.  The  fluid  is  vigorously  shaken,  the 
precipitate  in  the  form  of  a  white  paste,  finely  granulated,  is  collected  on  a 
filter  and  washed  with  saturated  solution  of  MgSO4,  to  remove  the  albumin. 
If  the  precipitate  left  on  the  filter  is  coloured,  it  is  dissolved  in  a  dilute 
solution  of  MgSO4  or  NaCl,  and  reprecipitated  as  before.  This  operation  is 
repeated  several  times,  and  then  completed  in  the  manner  described  for  the 
estimation  of  fibrinogen. 

Estimation  of  Serum  Albumin. — The  serum  saturated  with  magnesium 
sulphate,  from  which  the  paraglobulin  has  been  removed  by  filtering,  can  be 
used  again  for  the  quantitative  estimation  of  serum  albumin.  This  can  be 
precipitated  by  the  addition  of  a  small  amount  of  0*5- 1  per  cent  of  acetic 
acid.  To  purify  it,  dissolve  again  in  water,  and  reprecipitate  with  solution 
of  ammonium  sulphate.  The  further  treatment  is  the  same  as  that  described 
above  for  fibrinogen.  Serin  is,  however,  more  frequently  calculated  by 
difference,  as  follows : — In  one  portion  of  serum  the  paraglobulin  is 
estimated  by  the  preceding  method,  and  in  a  second  portion,  equal  to  the 


v  THE  BLOOD :  PLASMA  129 

first,  the  total  weight  of  the  proteins  coagulated  by  alcohol  or  by  heat.  The 
percentage  amount  of  serum  albumin  can  be  calculated  from  the  difference 
t>etweeii  the  two  values. 

Estimation  of  Sero-mucoid. — I.  To  prepare  and  simultaneously  estimate 
sero-mucoid,  Zanetti  used  the  same  method  Morner  employed  for  ovo-mucoid. 
The  proteins  are  first  precipitated  from  a  given  amount  of  blood  serum 
diluted  witli  two  volumes  of  10  per  cent  NaCl  solution,  by  coagulation,  after 
previous  acidification  with  acetic  acid.  The  filtrate  is  evaporated  on  the 
water  bath  to  a  reduced  volume,  and  is  then  treated  with  alcohol.  To 
purify  the  precipitate  obtained,  which  consists  of  sero-mucoid,  it  is  again 
dissolved  in  water,  and  reprecipitated  with  alcohol.  This  operation  is 
repeated  five  or  six  times,  till  a  very  slightly  coloured  precipitate  is  obtained,, 
which  can  be  collected  on  a  filter  that  has  been  previously  dried  and 
weighed.  After  repeated  washing  with  ether,  the  substance  is  dried  in  vacuo 
over  sulphuric  acid  till  the  weight  is  constant.  The  sero-mucoid  appears  as 
a  light  straw-coloured  powder.  It  is  somewhat  hygroscopic,  dissolves  in 
warm  water,  and  gives  all  the  reactions  of  mucoid  substances.  Its  property 
of  reducing  Fehling's  solution  after  previous  boiling  with  hydrochloric  acid,, 
led  Zanetti  to  term  it  gluco-protein. 

III.  The  various  proteins  differ  little  in  their  percentage  com- 
position, and  are  probably  derived  from  the  molecular  complex 
into  which  the  different  nuclei  or  groups  of  atoms  have  entered 
in  different  relations.  In  fact,  when  broken  up  by  steam  at  high 
pressure,  or  by  prolonged  boiling  with  dilute  alkali  or  mineral 
acids,  they  invariably  yield  the  same  products,  viz.  ammonia, 
hydrogen  sulphide,  and  a  series  of  ammo-acids,  among  which 
tyrosine,  leucine,  and  asparaginic  acid  are  always  present.  Since 
tyrosine  is  a  compound  of  the  aromatic  series,  and  leucine  and 
asparaginic  acid  are  two  bodies  of  the  fatty  series,  we  may  conclude 
that  atomic  groups  of  both  series  enter  into  the  protein  molecule. 

Within  the  body,  however,  in  consequence  of  the  metabolic 
activity  of  the  living  elements  of  the  tissues,  the  proteins  give 
rise  to  a  large  number  of  decomposition  products,  which  are 
either  simple  waste  products,  destined  as  such  to  be  eliminated 
by  the  various  excretory  organs,  or  products  of  internal  secretion, 
destined  to  fulfil  other  functions  and  to  undergo  further  trans- 
formations before  they  are  eliminated.  For  the  most  part  these- 
consist  of  the  constituents  of  urine,  which  are  excreted  by  the 
kidneys,  among  the  most  important  being  creatine,  creatinine,  uric 
acid,  hippuric  acid,  carbamic  acid,  and  urea.  All  these  are  nitro- 
genous compounds,  and  are  therefore  derived  from  retrogressive 
or  katabolic  metamorphoses  of  the  proteins. 

As  these  waste  products  are  promptly  eliminated  as  fast  as 
they  reach  the  blood  plasma,  they  can  obviously  exist  there  only 
in  very  minute  quantities.  As  a  matter  of  fact,  urea  and 
ammonia  are  the  sole  constituents  of  urine  that  can  be  isolated 
from  blood  serum,  urea  only  in  an  amount  of  which  the  maximum 
does  not  exceed  O05  per  cent  (I.  Munk),  ammonia  in  an  average 
amount  of  O79  mgrni.  to  each  100  grins,  of  blood  (Beccari).  Creatine 
and  uric  acid  are  found  in  much  smaller  quantities;  hippuric 

VOL.  I  K 


130  PHYSIOLOGY  CHAP. 

acid  least  of  all,  since,  as  will  be  shown  later  on,  the  greater  part 
at  any  rate  is  formed  by  a  synthetic  process  in  the  kidneys. 
Under  pathological  conditions,  however,  when  the  renal  function, 
is  profoundly  affected  or  abolished  (uraemia),  as  also  in  grave'' 
alterations  of  the  blood  (leucaemia),  besides  these  nitrogenous 
products  others,  which  are  normally  present  in  the  urine  in 
exceedingly  small  quantities,  e.g.  the  xanthine  bases  (Scherer),  can 
be  demonstrated  in  the  serum. 

IV.  Besides  the  nitrogenous  compounds,  neutral  fats  are  found 
in  the  blood  serum,  emulsified  to  minute  drops  which  can  readily 
be  extracted  with  ether.  The  amount,  which  under  normal  con- 
ditions does  not  exceed  Q'l-0'2  per  cent,  increases  conspicuously 
after  a  fatty  meal,  giving  a  milky  appearance  to  the  serum,  and 
it  may  reach  or  exceed  1  per  cent  of  the  total  quantity  of  blood 
(Kohrig) ;  whereas  in  the  fasting  state  only  minute  traces  remain 
(Pfeiffer).  It  is  thus  obvious  that  the  fats  of  the  blood  are  derived 
principally  from  the  fatty  substances  taken  in  with  the  food.  In 
certain  morbid  conditions,  however  (alcoholism,  diabetes,  diseases 
of  the  bone  marrow),  the  amount  of  fat  in  the  blood  plasma  may 
increase  so  much  that  the  serum  assumes  a  milky  aspect  (lipaemia) 
as  after  a  meal  that  has  been  rich  in  fats.  It  is  therefore  probable 
that  the  fat  of  the  blood  is,  even  under  normal  conditions,  derived 
to  a  lesser  extent  from  what  is  eliminated  or  liquefied  from  the 
adipose  tissues. 

In  addition  to  neutral  fats,  blood  serum  contains  soaps, 
lecithin,  and  cholesterin  (Hoppe-Seyler).  These  form  part  of  the 
products  of  pancreatic  digestion,  hence  they  also  come  in  part 
from  the  digestive  canal. 

A  third  group  of  organic  substances  also  found  in  serum  are 
conventionally  comprised  under  the  term  carbohydrates :  glucose, 
glycqgen,  lactic  acid.  There  is  yet  another  reducing  substance, 
which  is  not  fermentable ;  it  contains  phosphorus,  is  capable  of 
extraction  with  ether,  and  gives  all  the  reactions  of  jecorin 
(Jacobson).  Lastly,  there  is  a  small  quantity  of  animal  gum 
(Freund). 

The  most  important  of  all  these  substances  is  certainly  glucose, 
which  originates  partly  direct  from  the  food,  partly  from  the 
digestive  transformation  of  alimentary  starch,  partly  from  the 
glycogen  of  the  liver  and  muscles.  The  quantity  of  glucose  in 
the  blood  is  independent  of  the  nature  of  the  food,  because,  as  we 
shall  see  later,  nearly  all  the  glucose  absorbed  from  the  intestine 
is  stored  up  in  the  liver  in  the  form  of  glycogen  (liver  starch). 
The  amount  of  glucose  found  in  normal  human  blood  varies  from 
O'lO  to  0'15  per  cent  (Otto);  but  under  abnormal  conditions  it 
may  reach  0'3  per  cent  or  more.  It  is  at  a  maximum  during  post- 
digestive  absorption  in  the  blood  of  the  portal  veins,  while  during 
inanition  it  is  most  abundant  in  the  blood  of  the  hepatic  veins. 


THE  BLOOD:   PLASMA 


131 


The  small  amount  of  glycogen  that  can  be  demonstrated  in 
blood  serum  (Pavy)  probably  derives  from  the  disintegration 
of  the  leucocytes,  which,  as  stated,  contain  a  certain  amount 
of  it. 

The  constant  presence  of  lactic  acid  in  blood  serum  is  in- 
dependent of  the  ingestion  of  carbohydrates,  while  it  is,  on  the 
contrary,  partly  dependent  on  the  flesh  food.  The  amount  of 
lactic  acid  found  in  the  blood  of  dogs  during  absorption  after  a 
full  meat  meal,  may  amount  to  Q'3-0'5  per  cent,  while  after 
forty-eight  hours'  starvation  it  diminishes  to  017  per  cent 
(Gaglio).  Lactic  acid,  as  we  shall  see,  is  one  of  the  decomposition 
products  of  proteins,  elaborated  either  by  the  blood  corpuscles  or 
by  the  living  elements  of  the  various  tissues. 

V.  The  mineral  constituents  of  blood  plasma  occur  partly  in 
the  form  of  free  salts,  partly  in  combination  witli  the  proteins, 
from  which  they  cannot  be  separated  by  simple  dialysis. 
What  the  true  physical  and  chemical  conditions  within  the 
plasma — the  reciprocal  relations  and  the  fixed  or  labile  bonds 
between  the  various  mineral  constituents  on  the  one  hand,  and 
the  various  proteins  on  the  other — may  be,  is  one  of  the  most 
difficult  problems  in  the  chemical  physiology  of  to-day,  and  its 
solution  is  the  aim  of  various  physico-chemical  researches,  of 
which  this  is  not  the  place  to  speak. 

If  combustion  is  employed  to  isolate  the  inorganic  matters 
from  the  dry  residue  of  serum,  the  ash- will  be  found  to  contain 
a  large  amount  of  sulphates,  derived  from  the  combustion  of  the 
sulphur  of  the  proteins,  which  are  not  among  the  mineral  con- 
stituents of  true  plasma.  In  the  same  way,  if  care  be  not  taken 
before  the  serum  is  incinerated  to  remove  the  lecithin  by  ether, 
there  will,  owing  to  combustion  of  its  phosphates,  be  an  excessive 
increase  in  the  phosphates  of  the  ash. 

Setting  aside  for  these  reasons  the  sulphates  and  phosphates 
found  in  the  ash  of  serum,  the  results  of  the  different  analyses 
made  for  man  and  for  the  other  mammals  harmonise  perfectly  for 
the  rest  of  the  constituents,  as  appears  from  the  following  table  : — 


In  1000  parts  of  si'runi. 

Human  Blood 
(C.  Schmidt). 

Pig's  Blood 
(Bunge). 

Calf's  Blood 
(Bunge). 

Average  of  the 
three  analyses. 

K20  . 

Na20 
Cl      . 
CaO  . 
MgO. 

0-394 
4-290 
3-612 
0-155 

0-101 

0-273 
4-272 
3-611 
'0-136 
0-038 

0-234 
4-351 
3-717 
0-126 
0-045 

0-300 
4-304 
3  -646 
0-139 
0-061 

8-552 

8-330 

8-473 

8-450 

132  PHYSIOLOGY  CHAP, 

These  figures  show  that  sodium  chloride  is  by  far  the  most 
abundant  constituent  of  the  ash  of  serum.  It  is  held  in  simple 
solution  in  the  plasma  or  in  the  form  of  highly  unstable  compounds,,, 
for  when  serum  is  dialysed  in  distilled  water,  osmotic  equilibrium 
between  the  two  fluids  is  soon  arrived  at  in  regard  to  the  chlorine. 

The  greater  part  of  the  sodium  of  the  ash  exists  in  the  form  of 
bicarbonate  (Giirber)  in  the  plasma,  a  lesser  amount  being  com- 
bined with  phosphoric  acid  in  the  form  of  di-sodic  phosphate. 

It  should  be  noted  that  potassium  salts  predominate  in  the 
corpuscles,  sodium  salts  in  the  plasma. 

The  osmotic  pressure  of  plasma  depends  largely  upon  the  sum 
of  the  inorganic  matters  which  it  contains ;  it  is,  as  we  shall  see, 
of  great  importance  in  the  metabolic  exchanges  between  corpuscles- 
and  plasma,  and  between  plasma  and  tissues. 

The  blood  gases,  as  a  whole,  represent  a  very  small  part  of  the 
weight  of  the  blood  (0'10-0'15  per  cent).  They  are  oxygen,  carbonic 
acid,  nitrogen,  and  also  argon.  The  two  first  occur  principally  in 
combination,  the  two  last  in  simple  solutions.  Nitrogen  and  argon 
are  not  known  to  fulfil  any  function  in  the  animal  economy ;  on 
the  other  hand  (as  we  shall  find  in  discussing  the  Chemistry  of 
Kespiration),  oxygen  and  carbonic  acid  are  of  capital  importance. 
Here  we  must  confine  ourselves  to  stating  that  the  combinations- 
winch  they  form  of  oxygen  with  haemoglobin,  and  of  carbonic  acid 
with  haemoglobin  and  the  alkalies,  are  very  unstable,  so  that  it  ia 
possible  with  the  vacuum  to  separate  and  estimate  volumetrically 
the  whole  of  the  gases  contained  in  the  blood. 

VI.  After  ascertaining  the  several  constituents  of  the  blood 
corpuscles  and  blood  plasma,  it  is  easier  to  marshal  the  data 
referring  to  the  solution  of  the  problem  of  Blood  Coagulation,  a 
problem  which  is  indeed  one  of  the  most  difficult  in  physiological 
chemistry. 

Although  this  problem  has  of  late  years  been  treated  with 
extraordinary  acumen  by  a  number  of  observers  (e.g.  A.  Schmidt 
in  particular),  we  cannot  at  present  claim  to  have  established 
any  theory  that  is  universally  acceptable  in  all  its  details. 

In  studying  the  phenomena  of  coagulation  it  is  well  to  treat 
the  different  questions  and  problems  involved  as  if  each  were 
separate  and  distinct  in  itself. 

(a)  The  first  problem  that  presents  itself  is  why,  i.e.  under 
what  conditions,  the  blood,  which  remains  fluid  so  long  as  it 
circulates  within  the  vessels,  coagulates  spontaneously  soon  after  it 
leaves  them.  This  question  was  attacked  by  Hewson  in  the 
eighteenth  century,  while  Briicke  solved  it  more  completely  in 
1857. 

Clotting  does  not  depend  upon  the  cooling  of  the  blood,  for 
when  frozen  before  coagulation,  it  is  found  on  thawing  still  to  be 
fluid,  and  clots  soon  after  in  the  usual  manner.  Cooling,  therefore. 


v  THE  BLOOD:   PLASMA  133 

retards  coagulation ;  as  shown  by  the  fact  that  when  the  shed 
blood  is  warmed  to  the  ordinary  temperature  of  the  animal 
(3T-380  C.)  it  clots  more  rapidly  (Hewson). 

Coagulation  does  not  depend  on  the  quiescence  of  the  blood 
drawn  from  the  vein,  for  some  of  the  blood  in  the  dog's  heart 
13  hours  after  death  (Hewson),  and  the  whole  of  a  dog's  blood 
6J-7J  hours  after  death  by  asphyxia,  is  found  to  be  fluid. 
Again,  the  blood  in  a  tortoise  heart  that  has  been  ligatured  or 
excised,  and  kept  at  a  temperature  of  approximately  zero,  is  found 
to  be  fluid  7-8  days  after  (Brlicke). 

Nor,  again,  does  coagulation  depend  on  contact  with  the  air  or 
its  oxygen,  for  the  blood  received  under  a  bell-jar  filled  with 
mercury  coagulates,  and  the  blood  of  a  tortoise  does  not  clot  after 
injection  of  a  considerable  quantity  of  air  into  its  vessels  (Briicke). 

Contact  with  the  normal,  living  walls  of  the  vessels  inhibits 
coagulation  of  the  circulating  blood,  while  the  injury  or  death  of 
the  vascular  endotheliuni,  or  the  introduction  of  any  foreign  body 
into  the  vessels  (e.g.  a  needle  pushed  through  the  heart  of  a  living 
tortoise),  make  the  blood  coagulate  (Briicke). 

When  the  blood  is  received  directly  into  a  vessel  greased 
with  vaselin,  or  under  oil,  it  neither  adheres  to  it  nor  clots,  nor 
does  it  on  stirring  with  a  well-greased  glass  rod.  On  the  other 
hand,  it  coagulates  readily  when  stirred  with  a  rod  that  has 
not  been  greased,  or  when  any  foreign  body  is  introduced  which 
the  blood  can  adhere  to.  It  is  therefore"  highly  probable  that  the 
circulating  blood  remains  fluid  because  its  morphological  elements 
d.o  not  adhere  to  the  normal  endotheliuni  of  the  vessels,  and  that 
a  thrombus  is  formed  whenever  such  adhesion  becomes  possible 
by  degeneration  of  the  endotheliuni  (Durante)  or  other  morbid 
lesions  of  the  internal  walls  of  the  vessels  and  heart,  as,  e.g., 
in  phlebitis,  endocarditis,  endarteritis,  atheromatosis  (Freund, 
1886). 

(&)  The  second  question  to  be  solved  is  the  determination  of 
the  immediate  cause  of  coagulation,  i.e.  why  the  simple  adhesion 
of  certain  elements  of  the  blood  to  foreign  bodies,  or  to  the  injured 
endotheliuni,  should  give  rise  to  the  formation  of  fibrin. 

In  this  connection  we  have  a  series  of  striking  observations, 
which  show  plainly  that  the  formation  of  the  fibrin  clot  is  intimately 
bound  up  with  the  functional  alteration  or  destruction  of  the 
formed  elements  of  the  blood,  more  particularly  of  the  leucocytes, 
which,  as  we  have  seen,  are  very  unstable,  and  easily  damaged  by 
every  imaginable  external  physical  influence.  Simple  contact  with 
foreign  bodies,  to  which  they  may  adhere,  is  sufficient  to  provoke 
secretion  in  the  plasma  of  substances  able  to  produce  clotting. 

This  theory,  proposed  by  Addisoii  (1841)  and  Beale  (1864),  was 
clearly  demonstrated  for  the  first  time  by  Mantegazza  (1876). 
Wherever  a  thrombus  is  produced  within  the  vessels  or  the  heart, 


134  PHYSIOLOGY  CHAP, 

the  fibrinous  clot  is  seen  under  the  microscope  to  be  infiltrated 
with  more  or  less  altered  leucocytes. 

If  a  silk  thread  is  introduced  into  the  interior  of  a  large  vein/ 
and  carefully  drawn  out  after  some  time  and  investigated  under 
the  microscope,  a  fine  coagulum  will  be  seen  to  have  formed  round 
the  thread,  which  is  denser  in  the  places  where  the  leucocytes 
enclosed  among  the  filaments  are  most  numerous  (Mantegazza). 

When  the  coagulation  of  a  small  drop  of  blood  plasma  i& 
watched  under  the  microscope,  the  fibrin  threads  of  which  it  is 
constituted  are  often  seen  to  spread  out  like  rays  from  a  centre, 
which  is  formed  by  a  leucocyte  or  a  collection  of  disintegrated 
platelets  (Eanvier,  Hayem,  Bizzozero). 

On  separating  the  plasma  of  horse's  blood  by  cooling,  and 
filtering  it  through  a  triple  layer  of  filter-paper,  it  can  be  obtained 
entirely  free  of  formed  elements.  In  this  case  it  will  be  seen  that 
the  plasma  left  at  the  temperature  of  the  environment  may  remain 
fluid  even  after  twenty-four  hours.  But  if  even  a  nominal  amount 
of  a  watery  extract  of  leucocytes,  or  a  little  blood  serum  containing 
leucocytes,  be  added,  clotting  at  once  occurs  (A.  Schmidt). 

Certain  morbid  pathological  transudations  behave  exactly  like 
the  cell-free  plasma,  e.g.  hydrocele,  or  pericardial  fluid,  which  are 
free  from  formed  constituents,  and  are  of  a  similar  composition  to 
plasma.  Left  to  themselves,  they  remain  fluid  for  an  unlimited 
time,  but  coagulate  so  soon  as  a  little  blood  clot  or  serum  is  added 
(Buchanan,  1835). 

When  entirely  freed  from  corpuscles  by  prolonged  and 
energetic  centrifuging,  the  plasma  separated  from  peptonised 
blood  not  only  does  not  coagulate  spontaneously,  but  will  not  do 
so  on  the  addition  of  water,  or  when  a  stream  of  carbonic  acid  is 
passed  through,  as  is  the  case  with  peptonised  plasma  not  wholly 
deprived  of  leucocytes.  But  if  a  little  clump  of  leucocytes  and 
platelets  obtained  by  centrifuging  be  added,  coagulation  at  once 
occurs  (Fano). 

The  theory  of  Hayem  and  Bizzozero  to  the  effect  that  coagula- 
tion depends  essentially  on  injury  or  destruction  of  the  blood- 
' platelets,  does  not  contradict  the  preceding  theory,  by  which  it  is 
associated  with  the  injury  or  destruction  of  leucocytes.  Assuming 
(as  seems  probable  from  the  researches  of  Lilienfeld,  referred  to  in  the 
last  chapter)  that  blood-platelets  are  derived  from  leucocytes  and 
represent  the  mass  of  their  nuclei,  the  two  points  of  view  are  quite 
in  harmony,  and  may  be  combined  and  enlarged  into  a  single  theory. 
A.  Petrone  has  recently  discovered  that  the  blood  coagulates 
firmly  and  rapidly  in  the  early  stages  of  pyrogallic  acid  poisoning 
(1  per  cent  solution  introduced  per  rectum  for  dogs  and  rabbits), 
while  the  platelets  are  not  injured,  and  even  appear  to  increase, 
the  erythrocytes  only  suffering  marked  deterioration.  The 
analytical  investigation  of  this  complex  intoxication  has,  however, 


v  THE  BLOOD:   PLASMA  135 

been  too  incomplete  to  make  it  the  basis  of  a  theory  so  opposed  to 
observations  and  experiments  conducted  on  simpler  and,  therefore, 
more  convincing  lines.  Lymph  contains  neither  erythrocytes  nor 
platelets,  as  shown  by  Fano,  and  yet  it  coagulates. 

(c)  The  third  point  in  the  theory  of  coagulation  is  to  determine 
on  which  or  what  chemical  constituents  of  the  blood  the  formation 
of  fibrin  depends,  since  it  is  insoluble  and  cannot,  therefore,  pre- 
exist as  such  in  the  blood. 

It  was  pointed  out  by  Hewson  (1770)  and  by  G.  Miiller  (1832) 
that  the  mother-substance  of  fibrin  is  derived,  not  from  the 
corpuscles,  but  from  the  constituents  of  the  blood  plasma.  Hewson 
was  the  first  to  obtain  salted  plasma  comparatively  free  from 
corpuscles,  and  noted  that  it  formed  a  white  clot  on  the  simple 
addition  of  water.  Joh.  Miiller  succeeded  in  filtering  frog's  blood, 
in  which  coagulation  had  been  retarded  with  a  sugar  solution, 
thus  separating  the  corpuscles  that  remained  on  the  filter  from  the 
colourless  plasma  of  the  filtrate,  and  obtained  in  the  latter  a  clot  of 
pure  fibrin.  The  first,  however,  to  demonstrate  that  coagulation 
is  a  change  of  chemical  state  in  a  substance  of  the  plasma  which 
he  termed  fibrinogen  (which  is  found  isolated  in  the  transudates 
already  referred  to,  and  mixed  with  serum  globulin  and  serum 
albumin  in  the  plasma),  was  A.  Schmidt. 

He  assumed  that  two  elements  enter  into  the  composition  of 
fibrin :  fibrinogen  (the  fibrinogenic  substance),  and  paraglolulin 
(fibrinoplastic  substance),  explaining  by'  this  the  observations  of 
Buchanan,  as  cited  above.  Subsequently,  however,  it  was  shown 
by  Hammarsten  (1875),  and  confirmed  by  others,  that  paraglobulin 
takes  no  part  in  the  formation  of  the  clot,  since  the  blood  contains 
an  equal  amount  both  before  and  after  coagulation,  and  since  a 
solution  of  pure  fibrinogen  obtained  from  salt  plasma  can  yield  a 
fibrinous  clot  011  adding  a  little  watery  extract  of  serum,  which  is 
quite  free  from  paraglobulin. 

(d}  A  fourth  problem  :  granted  that  fibrinogen  is  able  to  produce 
fibrin  by  a  change  in  its  chemical  state,  it  must  be  determined  in 
what  this  change  consists. 

This  question  is  attacked  in  the  later  work  of  Hammarsten, 
Arthus,  Lilienfeld,  Car  bone  and  others. 

Some  hold  the  coagulation  of  blood  to  be  a  phenomenon  analogous 
to  the  curdling  of  milk.  The  substance  derived  from  the  corpuscles 
which  excites  coagulation  splits  up  the  fibrinogen  into  two  new 
globulins — thrombosin,  which  is  insoluble,  and  changes  into  fibrin  : 
and  fibrinoglobulin,  which  remains  in  solution  in  the  plasma. 
During  this  splitting  of  the  fibrinogen,  i.e.  hydration,  the  chemical 
association  of  water  with  the  proteins  occurs.  A.  Schmidt 
has  recently  shown  that  pure  horse's  plasma,  dried  before  coagula- 
tion, weighs  about  2  per  cent  less  than  an  equal  amount  of  the 
same  plasma  dried  after  coagulation. 


136  PHYSIOLOGY  CHAP. 

The  presence  of  a  certain  amount  of  soluble  and  readily 
ionisable  lime  salts  in  the  plasma  seems  essential  to  coagulation,  or 
to  the  transformation  of  the  soluble  thrombosin  into  fibrin,  which 
precipitates  as  a  clot.  The  reason  why  oxalates  and  sodium 
fluoride,  even  in  small  doses,  render  plasma  incoagulable  lies  in  the 
fact  that  they  precipitate  the  calcium  salts  dissolved  in  the  plasma, 
and  thus  hinder  the  conversion  of  thrombosin  into  fibrin  by 
combination  with  the  lime  salts.  Fibrin  accordingly  would  be  a 
compound  of  calcium  with  thrombosin,  and  comparable  as  such 
with  the  soluble  curd  which  is  a  calcium  compound  of  paracasein. 
Just  as  milk  casein  splits  under  the  action  of  the  rennet  ferment 
into  paracasein  and  a  special  albumose,  so  fibrinogen  splits  up 
during  blood  coagulation,  two-thirds  of  it  forming  thrombosin  and 
one-third  fibrinoglobulin.  As  paracasein  in  combination  with  lime 
forms  curd,  so  thrombosin  in  the  same  combination  produces 
fibrin  (Arthus,  Lilienfeld). 

To  this  ingenious  parallel  between  the  clotting  of  blood  and 
that  of  milk,  the  objection  has  been  raised  that  even  if  fibrin 
always  contains  lime,  it  is  no  richer  in  lime  than  is  the  fibrinogen ; 
hence  it  cannot  be  assumed  that  fibrinogen  takes  up  lime  from  the 
plasma  in  its  transformations  into  fibrin. 

Others  on  the  contrary  affirm,  perhaps  more  reasonably,  that 
coagulation  is  produced  by  a  simple  splitting  of  the  fibrinogen  into 
a  less  soluble  body  that  precipitates  (fibrin),  and  another  that  is 
soluble  (fibrin  globulin)  which  remains  in  the  serum ;  the  presence 
of  lime  seems  indispensable,  not  to  this  reaction  directly,  but  to  the 
production  or  the  activity  of  the  fibrin  ferment. 

In  any  case  it  is  undeniable  that  the  presence  of  calcium  in 
plasma  is  essential  to  coagulation,  even  if  its  precise  action  is  still 
undetermined. 

(e)  Another  question  to  be  solved  relates  to  the  chemical  form 
of  the  calcium  when  it  participates  as  an  indispensable  factor  in 
coagulation. 

Some  hold  that  it  intervenes  as  a  phosphate,  more  correctly  as  a 
tricalcic  phosphate,  and  think  that  as  it  is  insoluble  in  water,  it 
remains  dissolved  in  the  plasma  in  combination  with  the  proteins ; 
Arthus,  however,  demonstrated  that  insoluble  lime  salts  are  useless, 
and  that  the  presence  of  soluble  salts  is  essential.  Sabbatani 
further  demonstrated  that  it  is  not  merely  the  soluble  salts,  but 
also  the  ionisable  salts  of  calcium  that  are  always  present  in  plasma, 
which  are  indispensable. 

It  therefore  appears  probable  that  calcium  intervenes  in 
coagulation  in  virtue  of  its  characters  and  chemical  properties  as  a 
kat-ion,  combining  with  those  elements  that  have  the  function  of 
an-ions,  perhaps  with  the  leuconuclein  of  Lilienfeld,  which  we 
shall  discuss  later. 

The   quantity   of  calcium   ions    adequate   to  produce    blood 


v  THE  BLOOD:   PLASMA  137 

coagulation,  unlike  that  required  in  milk  coagulation,  is  minimal, 
but  under  uniform  experimental  conditions  it  is  constant ;  we  thus 
have  a  critical  value  for  the  concentration  of  Ca-ions,  below  which 
the  blood  remains  indefinitely  liquid. 

On  the  one  hand,  accordingly,  all  physical  or  chemical  agents 
that  lower  the  concentration  of  the  Ca-ions  of  the  blood  below  the 
critical  value  provoke  incoagulability ;  on  the  other,  all  those 
agents  which  raise  it  above  the  said  value  favour  coagulation. 
Among  the  former  are  cold,  high  molecular  concentration,  small 
doses  of  reagents  which  form  almost  insoluble  salts  with  calcium 
(oxalates,  fluorides,  soaps,  carbonates,  alkaline  pyrophosphates), 
moderate  doses  of  reagents  which  with  lime  form  simple  salts  that 
are  sparingly  soluble  (di-sodic  sulphate  and  phosphate,  sodium 
bicarbonate),  small  doses  of  reagents  winch  with  lime  form 
compounds  that  are  little  ionisable  (tri-sodic  citrate,  sodic  meta- 
phosphate) ;  among  the  latter  are  heat,  dilution  with  water,  addition 
of  small  quantities  of  ionisable  lime  salts,  addition  of  reagents  that 
liberate  the  calcium  from  its  insoluble  or  little  dissociable  compounds. 

On  the  other  hand,  the  addition  of  small  quantities  of  calcium 
to  normal  blood  invariably  diminishes  coagulability  (Sabbatani, 
Eegoli),  and  it  was  only  the  inexact  interpretation  of  certain 
experiments  of  Dastre  and  Hammarsten  that  led  people  for  some 
time  to  believe  that  it  was  increased  by  the  same ;  the  addition 
of  a  moderate  quantity  much  delays  coagulation :  large  doses 
entirely  prevent  it  (Home). 

From  all  these  results  it  appears,  in  regard  to  the  concentration 
of  Ca-ions  in  the  blood,  that  we  must  assume  an  optimum  value 
for  coagulation  (lying  between  the  limits  of  the  physiological 
Variations  which  calcium  presents  in  normal  blood),  and  two 
critical  values,  minimal  and  maximal,  above  and  below  which  the 
blood  no  longer  coagulates. 

The  addition  of  lime  increases  coagulation  only  when  the  blood 
is  deficient  in  it. 

(/)  Next  conies  the  question  of  determining  by  what  process 
the  injury  or  dissociation  of  blood  corpuscles  leads  to  the  breaking- 
up  of  fibrinogen  into  fibrin  and  fibrin-globulin. 

A.  Schmidt  and  his  school  (Dorpat)  treat  blood  coagulation  as  a 
process  determined  by  an  enzyme  which  they  call  thrombin,  which  is 
derived  from  the  blood  corpuscles,  particularly  from  the  leucocytes 
and  platelets.  In  the  normal  state  these  contain,  not  the  ferment, 
but  a  zymogenic  substance,  pro-thrombin,  which  on  injury  or 
destruction  of  the  corpuscles  gives  rise  to  the  ferment  proper, 
tkrombin.  This  can  be  extracted  either  from  defibrinated  blood  or 
from  blood  serum,  by  absolute  alcohol,  which  precipitates  the 
protein  matters  with  the  ferment.  The  ferment  can  be  extracted 
from  the  mass  of  the  well-dried  and  pulverised  clot  by  making  a 
watery  extract. 


138  PHYSIOLOGY  CHAP. 

The  watery  extract  containing  thrombin  quickly  produces 
fibrinous  coagulation,  either  from  solutions  of  pure  fibrinogen, 
containing  a  small  amount  of  lime  salts  in  solution,  or  from  the' 
fluid  transudate  of  hydrocele.  When  injected  rapidly  in  moderate 
doses  into  the  vascular  system  of  an  animal,  instantaneous  death 
may  be  produced  by  diffused  thrombosis,  which  inhibits  the  circula- 
tion of  the  blood  (Edelberg). 

That  there  is  in  circulating  blood  no  thrombin  proper,  but 
only  pro-thrombin,  is  proved  by  the  fact  that  the  watery  extract 
has  no  coagulative  action  when  it  is  obtained  (as  above)  not  from 
defibrinated  blood  or  serum,  but  from  fresh  blood  received  direct 
from  the  vein  into  absolute  alcohol  (Jakowicki).  The  perfect 
ferment,  or  thrombin,  is  only  formed  when  the  blood-corpuscles 
have  been  injured  or  disintegrated. 

Thrombin  in  a  watery  solution  is  not  attacked  by  antiseptics ; 
on  warming  to  75°  C.  it  loses  all  its  enzyme  action ;  it  exhibits 
the  general  properties  of  the  globulins,  and  is  a  phosphorus-free 
protein. 

Thrombin  is  not,  however,  the  only  substance  derived  from 
leucocytes  which  is  able  to  determine  coagulation  by  the  trans- 
formation of  fibrin.  Besides  these  enzymes  there  are  other 
substances  (particularly  in  the  nuclei  of  leucocytes  and  the  proto- 
plasm of  blood-platelets)  which  can  produce  the  same  effect,  as  has 
recently  been  established  by  the  experiments  of  Lilienfeld. 

We  have  seen  that  the  fundamental  substance  of  the  nuclei  of 
leucocytes  is  a  highly  complex  structure,  which  is  termed  nucleo- 
histone  because  it  results  from  the  association  of  two  groups,  one  an 
acid  phosphorus  containing  leuconuclein,  the  other  basic,  with  the 
properties  of  albumoses.  Now  Lilienfeld  has  demonstrated  that 
not  only  leuconuclein  but  also  its  derivative,  nucleic  acid,  are 
capable  of  decomposing  fibrinogen  and  of  producing  fibrinous 
clotting  under  all  conditions  in  which  Schmidt's  thrombin  has  the 
same  action.  Hist  one,  on  the  other  hand,  not  only  does  not  excite 
clotting,  but,  like  other  albumoses,  has  anti-coagulative  properties, 
both  for  circulating  and  for  shed  blood. 

From  the  blood  that  is  rendered  incoagulable  by  histone  it  is 
possible  to  separate  a  histonised  plasma  that  is  highly  resistant, 
and  only  coagulates  on  the  addition  of  nucleic  substances.  The 
an ti- coagulating  substance  obtained  by  A.  Schmidt  from  the 
alcoholic  extract  of  lymph  glands,  which  he  called  cytoglobulin, 
corresponds  essentially  with  histone. 

Lilienfeld's  results  thus  tend  to  prove  that  coagulation  can 
occur  without  [fibrin  ferment,  through  the  action  of  the  nuclein 
substances  of  the  leucocytes  and  platelets ;  yet,  as  Carbone  shows, 
there  is  a  considerable  analogy  in  respect  to  the  production  of 
fibrin  ferment  between  the  theory  of  Schmidt  and  that  of 
Lilienfeld. 


v  THE  BLOOD:   PLASMA 

According  to  Schmidt,  we  have  a  zyniogen,  pro-throinbin, 
which  in  splitting  gives  rise  to  the  ferment  and  to  a  substance, 
the  nature  of  which  he  does  not  define,  which  arrests  the  splitting 
of  the  pro-thrombin ;  according  to  Lilienfeld,  we  have  nucleo- 
histone,  which  divides  into  leuconuclein  with  a  coagulating  action, 
and  histone  with  an  anti-coagulating  action.  It  seems  probable 
enough,  one  may  almost  say  certain,  from  the  researches  of 
Pekelharing,  that  the  ferment  and  the  zyrnogen  are  nucleo- 
proteins.  Finally,  according  to  Schmidt,  the  pro-thrombin  is 
transformed  into  thrombin  (ferment)  solely  by  the  action  of 
unknown  substances  which  he  terms  zymoplastic ;  according  to 
Pekelharing  zymogen  is  transformed  into  ferment  solely  by  the 
action  of  lime  salts,  and  Lilienfeld's  leuconuclein  becomes  active 
as  a  ferment  only  in  the  presence  of  calcium. 

To  sum  up,  it  is  admitted  that  the  exciting  agent  of  coagulation 
(fibrin-ferment,  thrombin)  is  a  derivative  of  nucleohistone,  a 
derivative  of  acid  character,  which  becomes  active  solely  in  the 
presence  of  calcium-ions  ;  we  may  therefore  represent  the  formation 
of  the  ferment  by  the  following  scheme : — 

Nucleohistone 
(paralyses  the  coagulating  action  of  leuconuclein) 

Leuconuclein.  Histone. 

(In  presence  of  Ca-ions  becomes  (Arrests  splitting  of  nucleoliistone 

a  coagulating  ferment.)  and  paralyses   action   of  leuco- 

nuclein.) 

The  predominance  of  one  or  other  of  these  three  substances  gives 
rise  to  various  normal  or  abnormal  states  of  the  blood,  which  can 
be  tested  after  the  injection  of  albumose,  or  substances  with 
similar  action. 

The  latest  researches  of  Morawitz  and  others  have  led  to  a 
more  exact  acquaintance  with  the  so-called  zymoplastic  substances, 
i.e.  substances  capable  of  accelerating  the  process  of  coagulation. 
Delezenne  had  already  observed  with  birds'  plasma  that  various 
extracts  of  organs  or  tissues  have  a  similar  action.  Morawitz 
has  indicated  the  active  principle  of  these  extracts  by  the 
name  of  thrombo-kinase,  which  he  considers  indispensable,  in 
addition  to  the  calcium  salts,  for  the  transformation  of  pro- 
thrombin  into  thrombin.  The  production  of  thrombokinase  is 
thus  a  general  property  of  protoplasm,  while  more  particularly 
characterising  the  leucocytes  of  birds  and  the  blood-platelets  of 
mammals. 

(#)  Lastly,  one  further  question  has  to  be  explained.  As 
under  normal  conditions  the  old  blood -corpuscles  are  continually 
breaking  up,  and  young,  new  cells  substituted  for  those  which 


140  PHYSIOLOGY  CHAP. 

perish,  how  is  it  that  thrombosis  does  not  occur  in  circulating 
blood,  since  both  fibrin  ferment  and  coagulative  nucleic  substances 
must  be  poured  into  the  plasma  on  the  disintegration  of  the 
corpuscles  ? 

This  question  has  not  at  present  been  adequately  considered. 

Fano,  on  the  strength  of  certain  ingenious  experiments, 
suggested  that  peptonised  blood  does  not  coagulate  because  it 
contains  an  anti-coagulating  substance  of  uncertain  nature,  which 
comes,  not  from  the  formed  elements  of  the  blood,  but  from  the 
other  tissues — seeing  that  the  addition  of  peptone  to  freshly-drawn 
blood  does  not  inhibit  its  coagulation.  A.  Schmidt,  in  pursuance 
of  this  theory,  subsequently  extracted  his  cytoylobulin,  which  has 
a  pure  anti-coagulative  action  (and  is  probably  identical  with 
historic),  from  the  lymph  glands  and  other  tissues — as  above  stated. 
On  the  ground  of  many  experiments,  he  maintains  that  the  liquid 
state  of  circulating  blood  must  be  regarded  as  a  function-  of  the 
living  cells  of  the  fixed  tissues,  with  which  the  blood  is  in 
continual  exchange.  These  receive  the  nutrient  matters  from  the 
blood,  and  return  to  it  the  products  of  their  metabolism,  including 
the  globulins  (the  mother  substance  of  fibrin)  and  cytoglobulin, 
which  obstructs  the  coagulative  action  of  the  ferment  that  con- 
stantly diffuses  in  the  blood  owing  to  the  disintegration  of  the 
nuclei  of  the  leucocytes.  When  the  blood  is  extracted  from  the 
vessels,  cytoglobulin  no  longer  pours  in,  while  thrombin,  owing  to 
the  rapid  alteration  of  the  leucocytes,  is  abundantly  present,  and 
coagulation  takes  place. 

The  latest  experiments  of  Lilienfeld  show  the  ease  with  which 
nucleohistone,  when  introduced  into  the  circulation,  breaks  up  by  a 
process  of  which  we  are  wholly  ignorant,  into  its  two  components, 
the  coagulating  leuconuclein,  and  the  anti-coagulating  historic, 
which  last  is  found  in  a  free  state  in  blood  drawn  off  immediately 
after  the  injection,  and  according  to  Wright  is  present  in  urine  also. 
Lilienfeld,  however,  makes  no  definite  suggestion  as  to  why,  under 
normal  conditions  of  circulating  blood,  the  anti-coagulative  action 
of  the  histone  always  outweighs  the  coagulative  action  both  of  the 
'  nucleic  substances  and  of  the  ferment,  even  when  the  latter  is 
present  in  great  quantities  in  the  plasma,  as  occurs  with  the 
innocuous  transfusion  of  defibrinated  blood  or  of  simple  serum. 

In  regard  to  this  and  other  phenomena,  which  call  for  more 
adequate  explanation,  we  cannot  at  present  feel  satisfied  with  the 
work  that  has  been  done,  or  the  theories  proposed,  in  reference  to 
blood  coagulation. 

The  latest  attempts  to  discover  why  the  blood  does  not  clot 
within  the  vessels,  admit  the  presence  of  an  anti-thrombin,  or 
substance  which  neutralises  the  action  of  the  small  amount  of 
thrombin  present  in  normal  blood. 

According  to  the  observations  of  Nolf  and  others,  the  incoagul- 


v  THE  BLOOD:   PLASMA  141 

ability  of  peptonised  blood  depends  on  the  fact  that  under  the 
action  of  albumoses  the  leucocytes  and  endothelial  vessels  pro- 
duce a  substance  which  gives  rise  in  the  liver  to  a  large  secretion 
of  anti-thrombin,  which  is  subsequently  poured  out  into  the 
circulatory  torrent. 

VII.  The  blood  plasma,  of  which  we  have  enumerated  the 
principal  constituents,  presents  as  a  whole  a  solution  of  organic  and 
mineral  substances,  which  are  partly  in  chemical  combination, 
partly  a  simple  mixture  in  which  the  corpuscles  are  suspended. 
After  the  physico-chemical  theory  of  solutions  had  been  established 
by  the  work  of  Pfeffer,  H.  de  Vries,  Kaoult,  Van't  Hoff  and 
Arrhenius,  the  method  was,  later  on,  applied  to  physiology.  The 
determination  of  molecular  concentration,  osmotic  pressure,  elec- 
trical conductivity  and  viscosity  in  the  blood  serum  and  other 
tissue  fluids  of  the  body,  is  now  of  some  importance,  since  it  has 
brought  out  certain  striking  facts  which  are  the  starting-point 
of  a  new  chapter  on  the  'physical  properties  of  blood  plasma. 

Let  us  commence  with  certain  theoretical  considerations. 

By  the  molecular  concentration  of  a  solution  we  mean  the 
number  of  dissolved  molecules  (irrespective  of  their  chemical 
nature)  in  relation  to  a  given  weight  of  solvent,  which  in  the  case 
of  the  organic  fluids  is  always  represented  by  water. 

Such  a  solution,  introduced  into  the  graduated  tube  of  a 
Dutrochet's  endosinometer,  in  connection  with  a  mercury  mano- 
meter, and  separated  from  the  solvent  by  a  semi -permeable 
membrane  (i.e.  one  which  permits  the  passage  of  the  solvent,  but 
not  of  the  substances  dissolved),  sets  up  a  current  through  the 
membrane  by  which  the  solution  is  more  and  more  diluted,  so  that 
the  manometer  column  rises  to  a  certain  height,  after  which  it 
remains  stationary.  The  pressure  then  recorded  by  the  manometer 
represents  the  osmotic  pressure  of  the  given  solution. 

Pfeffer  showed  experimentally  that  the  osmotic  pressure  is 
in  direct  ratio  with  the  molecular  concentration.  Given  this 
relation,  it  follows  that  when  the  osmotic  pressure  of  a  certain 
solution  is  known,  its  molecular  concentration  is  known  also,  and 
vice  versa. 

Perfect  osmotic  equilibrium  between  two  solutions  is  obtained 
each  time  that  the  solutions,  separated  by  a  semi-permeable 
membrane,  contain  the  same  number  of  molecules  in  the  same 
volume  of  water,  even  if  they  are  of  different  chemical  constitu- 
tion. Suppose,  for  instance,  a  solution  of  urea  and  one  of  sugar 
to  be  separated  by  a  membrane  that  is  permeable  to  water  but 
not  to  the  dissolved  substances..  So  long  as  one  of  the  two- 
solutions  contains  a  larger  number  of  molecules  dissolved  in 
the  same  volume  of  water  than  the  other,  there  will  be  a  diffusion 
of  water  from  the  more  dilute  to  the  more  concentrated  solution. 
This  diffusion  ceases  as  soon  as  the  number  of  molecules  in  the 


142  PHYSIOLOGY  CHAI>. 

two  solutions,  in  respect  of  the  same  volume  of  water,  becomes 
equal  for  the   two  fluids,  although    their   chemical   constitution 
remains  unlike,  since  the  one  contains  only  urea  and  the  other^ 
sugar. 

Solutions  which  are  of  equal  molecular  concentration,  and 
are  therefore  called  equi-molecular,  have  also  the  same  osmotic 
pressure  and  are  termed  isotonic  (from  lu-os,  equal,  and  TOI/OS, 
tension).  In  fact,  when  separated  by  a  semi-permeable  membrane 
they  are  found  to  be  in  osmotic  equilibrium. 

According  to  a  law  discovered  by  Eaoult  (1S82),  each  molecule 
of  any  substance  dissolved  in  a  given  quantity  of  water  lowers  the 
freezing-point  of  the  water  by  a  certain  and  always  constant 
degree,  so  that  the  lowering  of  the  freezing-point  depends  on  the 
number  of  molecules  dissolved,  and  not  upon  their  weight  or  their 
chemical  constitution.  The  determination  of  the  freezing-point 
of  different  solutions  is  termed  Cryoscopy,  and  the  difference 
between  the  freezing-point  of  the  solution  and  that  of  the  pure 
solvent  is  indicated  by  the  symbol  A. 

The  cryoscopic  method  serves  indirectly,  by  an  easy  technique, 
to  determine  the  molecular  concentration  and  the  osmotic  pressure 
•of  any  given  solution. 

The  salts  in  general  are  an  exception  to  Eaoult's  Law,  since 
their  solutions  indicate  a  higher  osmotic  pressure  than  that  which, 
according  to  the  law,  should  be  exerted  by  the  number  of  their 
molecules.  The  molecules  of  these  salts  behave  as  if  a  portion  of 
them  were  split  up.  This  led  to  Arrhenius'  hypothesis  of  the 
electrolytic  dissociation,  or  ionisation,  of  dissolved  saline  molecules 
— a  phenomenon  which  is  in  strict  relation  with  the  electrical 
conductivity  of  the  solutions  of  salts,  acids  and  bases,  which  are 
called  electrolytes,  as  distinguished  from  the  solutions  of  non- 
ionisable  molecules  which  do  not  conduct  electricity  well,  and  are 
known  as  anelectrolytes.  This  ionisation  again  is  in  relation  with 
the  electrolysis  which  can  be  verified  in  these  solutions  on  the 
passage  of  a  galvanic  current.  The  dissociation  of  the  molecules 
of  salts  increases  with  dilution  of  their  solutions. 

Such  in  a  few  words  is  the  modern  physico-chemical  theory  of 
solutions.  We  must  now  go  on  to  examine  some  of  the  most 
important  results  obtained  by  this  method  in  regard  to  the  osmotic 
pressure  and  molecular  concentration  of  blood  serum. 

These  investigations  were  initiated  in  Holland  by  Hamburger, 
and  continued  by  others. 

Hamburger's  method  is  founded  upon  the  resistance  offered  by 
erythrocytes  to  diffusion  of  their  haemoglobin  when  they  are  im- 
mersed in  a  hypotonic  solution,  i.e.  one  in  which  the  concentration 
is  less  than  isotonic.  He  sought  to  alter  the  molecular  concentra- 
tion of  the  circulating  blood  plasma,  in  order  then  to  study  its 
•effects  on  the  serum  collected  from  a  small  quantity  of  shed  blood. 


v  THE  BLOOD:   PLASMA  143 

On  introducing  into  the  veins  of  a  horse  seven  litres  of  a 
hypertonic  solution  (solution  of  higher  concentration  than  an 
isotonic)  of  5  per-  cent  sodic  sulphate,  he  saw  that  the  salt  was 
immediately  eliminated  by  the  excretory  organs,  the  hyper  tony  of 
the  blood  serum  lasting  only  for  a  few  moments  after  the  injection, 
although  analysis  of  the  same  serum,  when  once  more  isotonic, 
proved  it  still  to  contain  a  very  abnormal  quantity  of  sodium 
sulphate. 

Again,  he  found  that  the  serum  recovered  its  normal  osmotic 
pressure  in  a  very  short  time  after  the  intravascular  injection  of 
a  hypotonic  solution  of  0'5  per  cent  sodic  sulphate. 

He  further  found  that  the  rise  of  osmotic  pressure  in  the 
serum,  caused  by  the  anhydraemia  produced  artificially  by  the 
subcutaneous  injection  of  pilocarpin  and  eserin  (which  cause 
marked  loss  of  water  by  exaggerated  secretions  of  sweat  and 
saliva),  lasts  only  a  short  time,  as  also  the  hydraemia  occasioned 
by  copious  bleeding. 

Hamburger  concluded  from  these  facts  that  the  vascular 
system  has  the  property  of  maintaining  constant  the  osmotic 
pressure  of  the  plasma,  notwithstanding  the  most  varying  changes 
in  the  chemical  composition  of  the  blood. 

He  explained  this  fact  on  the  hypothesis  of  a  secretory 
property  of  the  vascular  endotheliuni,  which,  when  stimulated  by 
the  increase  or  decrease  of  the  osmotic  pressure  of  the  blood,  reacts 
by  a  rapid  reinstatement  of  isotony.  The  secretory  capacity  of 
the  capillary  endotheliuni  was,  as  we  shall  see,  experimentally 
confirmed  by  Heidenhain. 

Starting  from  these  results,  Winter  made  other  experiments 
with  the  cryoscopic  method.  He  found  that  the  freezing-point 
of  blood  serum  in  the  mammalia  which  he  investigated  was 
practically  constant.  Freezing  nearly  always  took  place  at 
-  0'55°  C.,  which  point  corresponds  to  that  of  a  solution  of  0'91  per 
cent  NaCl  in  distilled  water.  According  to  him,  therefore,  the 
osmotic  pressure  of  the  blood,  being  independent  of  species  and 
individual,  must  in  all  probability  depend,  like  temperature,  on 
the  general  conditions  of  the  mammalian  environment. 

The  0'9 1  per  cent  NaCl  is  not  hypertonic  for  erythrocytes  as 
some  believe,  but  is  much  nearer  their  isotonic  value  than  the 
solution  at  0'61  per  cent,  which  rather  represents  the  minimal 
limit  of  concentration  compatible  with  a  rough  anatomical  in- 
tegrity of  the  erythrocytes — apart,  that  is,  from  the  changes  in 
shape  which  they  undergo.  In  fact,  it  is  shown  by  the  observa- 
tions of  Hamburger,  Malassez  and  others  that  the  lowest 
concentration  of  a  solution  of  NaCl  at  which  the  erythrocytes 
resist  diffusion  of  their  haemoglobin  is  0'61  per  cent.  Even  the 
solution  of  NaCl  at  0'75  per  cent  which  for  a  long  time  was 
considered  physiological,  is  hypotonic.  For  man  we  must  take 


144 


PHYSIOLOGY 


CHAP. 


the  0'90  per  cent  solution  to  be  isotonic ;  and  although  Winter 
found  the  chlorides  contained  in  serum  to  be,  when  expressed 
in  terms  of  NaCl,  a  little  in  excess  of  this  figure — which  re- 
presents  the  extreme  limit  of  corpuscular  resistance  (Q-62-0'72 
per  cent) — it  must  be  remembered  that  the  osmotic  pressure  of 
the  blood  is  due,  not  only  to  the  chlorides,  but,  in  a  minor 
degree,  to  other  salts  and  organic  molecules,  so  that  the  result 
is  considerably  higher  than  it  would  be  for  the  chlorides  alone. 
On  the  other  hand  Winter  himself  demonstrated,  by  means  of 
cryoscopy,  that  on  dilution  of  the  serum  the  molecular  concentra- 
tion is  clearly  higher  than  that  previously  expected  from  the 
dilution,  which  he  attributes  to  dissociation  of  the  molecules  of 
NaCl.  From  these  observations,  that  is,  from  the  rich  sodium 
chloride  content  of  blood  serum,  and  from  the  ready  ionisation  of 
its  molecules,  Winter  was  led  to  consider  this  salt  as  the  com- 
pensating factor  in  disorders  of  the  osmotic  conditions  of  the 
blood  and  tissue  fluids  generally. 

These  results  of  Winter,  in  so  far  as  they  concern  the  relative 
constancy  of  the  freezing-point  of  blood  serum  in  mammalia,  are 
unsatisfactory  inasmuch  as  they  disagree  with  the  data  previously 
obtained  by  Hamburger  and  Gryns,  and  more  recently  by 
Bugarszky  and  Tangl,  and  Bottazzi  and  Ducceschi.  Here  are 
some  of  the  data  obtained  by  these  authors : — 


Hamburger. 


Gryns. 


Serum  of  horse 


ox 
?ig 


A  =0-596 
0-585 
0-620 
0-568 
0-647 
0-621 
0-605 


Serum  of  horse 


fowl 


=  0-549 
0-561 
0-520 
0-619 
0-624 
0-620 
0-600 


Bugarszky  and  Tangl. 
Serum  of  horse    . 


cat 
sheep 


Bottazzi  and  Ducceschi. 


:  0-527 
0-531 
0-532 
0-570 
0-605 
0-585 
0-601 
0-633 
0-613 
0-588 


Serum  of  frog 
„  toad 
„  tortoise . 

5>  »5  ' 

cock      . 
,,          hare 
dog 


A  =0-563 
0-761 
0-463 
0-485 
0-623 
0-564 
0-576 


Fano  and  Bottazzi  found  in  a  series  of  cryoscopic  observations 
that  the  osmotic  pressure  of  dog's  serum  presents  only  slight 
variations  from  a  mean  value  (higher  than  that  found  by  Winter), 
even  when  the  animal  has  been  subjected  to  the  most  various 
organic  injuries,  such  as  splenectomy,  asphyxia,  inanition,  anaemia 


v  THE  BLOOD:   PLASMA  145 

from  repeated  bleeding,  peptone  injection,  ligation  of  thoracic  duct, 
section  of  medulla  oblongata. 

These  results  exclude  the  hypothesis  of  a  special  regulatory 
apparatus  of  the  physical  conditions  of  the  blood,  since  they  are 
independent  of  the  nutrition  of  the  body,  and  the  functional  con- 
ditions of  the  circulatory  apparatus  and  nerve  centres.  It  is 
logical  to  assume  that  the  practical  constancy  of  the  osmotic 
pressure  of  the  blood  depends  on  the  mutability  of  the  physico- 
chemical  grouping  of  atoms,  whether  intra-  or  extra-cellular  (in 
the  tissue  fluids),  through  which  adjustment  to  the  disturbances 
of  osmotic  equilibrium,  and'  compensation,  are  readily  effected. 
Besides  the  ionisation  of  the  molecules  of  sodium  chloride  as 
demonstrated  by  Winter,  we  may,  according  to  Fano,  hold  that 
the  associations  and  dissociations  of  the  salts  with  the  proteins, 
and  the  polymerisations  and  depolyrnerisations,  come  into  play  in 
the  rapid  compensation  of  the  abundant  rise  or  fall  of  the  osmotic 
blood  pressure. 

Bottazzi's  latest  observations  on  the  osmotic  pressure  of  marine 
animals  prove  that  the  value  of  the  osmotic  pressure  of  the  blood 
is  more  or  less  related  to  the  general  environmental  conditions  of 
the  organism.  The  blood,  both  of  marine  invertebrates  and  also 
of  the  cartilaginous  fishes,  shows  an  osmotic  pressure  approximately 
equal  to  that  of  sea-water  (A  =  2'2  -  2'3).  In  Teleosteans  the 
independence  of  the  osmotic  conditions  of  the  tissue  fluids  from 
the  external  environment  of  the  organism  begins  to  appear.  Their 
blood  shows  an  osmotic  pressure  which  is  about  half  that  of  sea- 
water,  and  intermediate  between  that  of  the  cartilaginous  fishes  and 
of  the  higher  vertebrates,  which,  although  they  live  in  the  sea, 
make  use  of  aerial  respiration.  The  blood  of  these  last  exhibits  an 
osmotic  pressure  differing  little  from  that  of  the  higher  terrestrial 
vertebrates. 

The  special  conditions  which  determine  these  differences  have 
still  to  be  ascertained  experimentally. 

Bottazzi  and  Ducceschi  in  other  interesting  experiments 
endeavoured  to  determine  the  relations  between  the  resistance  of 
the  erythrocytes  to  diffusion  of  their  haemoglobin,  the  osmotic 
pressure  of  serum,  and  the  alkalinity  of  plasma  in  the  different 
classes  of  vertebrates.  Their  chief  conclusion  is  that  in  the 
blood  of  mammalia  a  certain  ratio  and  mutual  dependence 
between  all  three  factors  can  be  observed,  but  that  this 
ratio  or  correspondence  disappears  in  animals  with  nucleated 
red  corpuscles.  It  therefore  seems  probable  that  the  presence 
of  a  nucleus  makes  the  erythrocytes  to  a  certain  degree  in- 
dependent of  the  physico-chemical  factors  of  the  fluid  in  which 
they  live,  which  (from  a  teleological  standpoint)  may  tend  to 
maintain  their  integrity,  particularly  in  the  poikilothermic 
animals,  which  are  subject  to  perpetual  changes  of  external 

VOL.  I  L 


146  PHYSIOLOGY  CHAP. 

environment.  A  mechanical  explanation  of  the  greater  resist- 
ance of  nucleated  erythrocytes  to  the  diffusion  of  their  haemo- 
globin, even  in  very  dilute  solutions  of  sodium  chloride,  may",' 
according  to  these  authors,  consist  in  the  fact  either  that  the 
nucleus  of  the  cell  exerts  a  positive  chemotactic  influence  on 
the  haemoglobin  of  the  strorna,  or  that  the  haemoglobin  makes 
a  more  stable  combination  with  the  lecithin  of  the  stroma. 
In  any  case,  it  is  clear  from  these  results  that  the  resistance  of 
the  nucleated  corpuscles  is  neither  an  expression  nor  a  measure 
of  intracorpuscular  osmotic  pressure. 

In  a  series  of  publications  (1895-97)  Manca  (experimenting 
always  with  the  red  blood-corpuscles  of  mammalia,  i.e.  with  non- 
nucleated  erythrocytes)  sought  to  determine  the  relations  in  these 
between  vitality  and  osmotic  pressure,  in  order  to  distinguish  the 
physiological  from  the  purely  physical  factors  in  the  pheno- 
mena of  their  resistance  and  osmotic  exchanges  with  the  plasma. 
He  set  out  from  the  conclusions  of  Hamburger,  Limbeck,  and 
other  physiologists  and  pathologists,  who,  in  considering  the  varia- 
tions of  resistance  offered  by  the  erythrocytes  to  various  physio- 
logical and  pathological  conditions,  interpret  these  phenomena  as 
dependent  on  changes  in  their  vital  conditions,  and  affirm  that 
only  living  erythrocytes  obey  the  laws  of  osmosis  and  of  isotonic 
coefficients.  The  problem,  attacked  by  Manca  from  various  aspects,, 
led  to  a  consensus  of  results,  which  may  be  summarised  in  a  few 
words. 

In  experiments  made  with  the  venous  blood  of  dogs,  both 
before  and  after  prolonged  muscular  exertion,  he  found  that  the 
resistance  of  the  erythrocytes  (determined  by  Hamburger's  method) 
underwent  a  slight  but  constant  increase. 

Erythrocytes  treated  in  vitro  with  strong  doses  of  cocaine 
hydrochlorate,  strychnine  sulphate,  atropine  sulphate,  morphine 
hydrochlorate,  showed  less  resistance  than  the  normal,  but 
perfectly  obeyed  the  same  laws  that  govern  the  osmotic  exchanges 
of  normal  blood-corpuscles. 

The  resistance  of  the  corpuscles  left  to  themselves  outside  the 
body,  with  no  aseptic  precautions,  also  diminishes  gradually ;  but 
after  3-10  days  (when,  according  to  Hamburger,  they  must  be 
considered  as  dead)  they  react  to  solutions  of  NaCl  and  KC1  like 
normal  erythrocytes,  and  obey  the  same  laws  of  osmosis.  The 
erythrocytes  behave  towards  dilute  solutions  of  the  same  salts  in 
such  a  way  that  it  must  be  assumed  that  the  molecules  of  NaCl 
and  KOI  are  equally  dissociated  or  ionised,  and  that  the  erythrocytes 
are  either  impermeable  to  them  or  permeable  to  the  same  small 
extent. 

The  erythrocytes  of  the  blood  when  treated  in  vitro  with  even 
the  strongest  doses  of  chloroform,  and  those  from  the  blood  of 
animals  killed  with  chloroform,  show  a  lower  resistance  than  the 


v  THE  BLOOD:   PLASMA  147 

normal,  but  perfectly  obey  the  same  laws  that  govern  the  osmotic 
relations  of  normal  blood-corpuscles. 

In  a  series  of  experiments  which  Manca  undertook  with  the 
haematocrite  method,  using  solutions  of  NaCl,  KC1,  LiCl,  he 
confirmed  the  previous  results  obtained  with  the  colorimetric,  or 
Hamburger's  method,  even  when  the  blood  had  been  preserved  for 
two  or  three  months,  with  or  without  aseptic  measures,  or  even 
after  saturation  with  CO.  From  an  average  of  seven  experiments 
with  the  haematocrite,  undertaken  to  determine  the  degree  of 
concentration  o"f  NaCl  isotonic  with  the  serum  and  erythrocytes  of 
fresh  defibrinated  ox  blood,  he  found  that  it  corresponded  with  a 
value  of  0*82  per  cent,  a  figure  somewhat  lower  than  that  deter- 
mined by  the  cryoscopic  estimations  of  Winter,  Fano,  and 
Bottazzi. 

From  the  sum  of  Manca's  results,  it  seems  legitimate  .  to  con- 
clude that  the  so-called  phenomena  of  resistance  of  the  erythrocytes 
(at  any  rate  of  those  that  are  non-nucleated)  and  their  osmotic 
properties,  are  independent  of  their  vitality,  and  that  the  red 
corpuscles  behave  like  simple,  inorganic,  artificial  Traube's  cells, 
which  consist  of  semi-permeable  membranes. 

The  above  are  the  most  interesting  results  obtained  by  the 
experimental  analysis  of  the  osmotic  properties  of  the  plasma  and 
blood -corpuscles.  From  these  few  indications  it  would  appear 
that  we  cannot  as  yet  form  a  definite  physiological  opinion  on  this 
important  subject ;  it  did  not,  however,  seem  proper  to  omit  the 
matter  completely,  since  it  must  obviously  be  of  cardinal  importance 
in  a  not  distant  future. 

Three  methods  in  particular  /ire  to  be  recommended  for  the  determina- 
tion of  the  osmotic  pressure  of  blood-serum  and  erythrocytes — that  of  Ham- 
burger, founded  on  the  resistance  of  the  erythrocytes ;  the  cryoscopic,  or 
Raoult's  method,  founded  on  the  lowering  of  the  freezing-point ;  and  that  of 
Hedin  arid  Kcippe,  founded  011  the  determination  of  the  volume  of  the 
erythrocytes  by  means  of  the  haematocrite. 

Hamhuryer's  method  for  determining  the  osmotic  pressure  of  blood  serum 
is  based  on  the  examination  of  that  solution  of  NaCl  with  which  it  is 
isotonic.  The  erythrocytes  of  mammalia  will  only  part  with  their  haemo- 
globin when  the  serum  in  which  they  are  immersed  is  diluted  with  50-60  per 
cent  distilled  water.  Thus,  to  find  the  value  of  the  solution  which  gives  the 
exact  osmotic  pressure,  it  is  only  necessary  to  prepare  some  specimens  of  the 
serum  diluted  to  the  required  extent.  Take  six  numbered  test-tubes,  5  c.c.  of 
serum  being  added  to  each.  To  the  first  add  3*1  c.c.  distilled  water,  to  the 
second  3  c.c.,  to  the  third  2-9  c.c.,  to  the  fourth  2-8  c.c.,  to  the  fifth  2'7  c.c.,  and 
to  the  sixth  2'6  c.c.  Then  let  three  drops  of  defibrinated  blood  fall  into  each 
test-tube,  agitate  the  mixtures  and  centrifuge. 

It  is  known  experimentally  that  the  NaCl  solution  isotonic  with 
mammalian  blood,  thus  diluted,  fluctuates  between  0*55  and  0'65  per  cent. 
Pour  about  8  c.c.  of  the  following  solutions  of  NaCl  into  six  more  test-tubes 
similarly  numbered— 0'62,  0'61,  0'60,  0'59,  0;58,  and  0'57  per  cent.  Then,  as 
in  the  first  series,  let  three  drops  of  defibrinated  blood  fall  into  each  tube, 
.and  shake. 

After  two  hours  the  erythrocytes  will  have  sunk  to  the  bottom  in  all  the; 

VOL.  I  L  a 


148  PHYSIOLOGY  CHAP. 

test-tubes.      In  the  first  series  the  fluid  will  be  red  in  some,  colourless  in 
others. 

When,  e.y.,  they  are  red  in  the  test-tubes  to  which  3*1,  3'0,  and  2'9  c.c.  of 
water  have  been  added,  and  colourless  in  the  rest,  the  result  works  out  as'/ 
follows  : — The  mixture  of  5  c.c.  serum +  2*9  c.c.  water  shows  diffusion  of  blood 

Slgment,  while  the  mixture  of  5  c.c.  serum  +  2*8  c.c.  water  remains  colourless, 
n  examining  the  second  set  of  test-tubes,  the  fluid  is  seen  to  be  tinted  in  a 
.saline  solution  of  0'58  per  cent  and  in  the  weaker  solutions,  while  the  contents 
of  the  tubes  with  the  stronger   solutions,  0'59,  O60  per  cent,    etc.,  remain 
tintinged. 

The  mixture  of  5  c.c.  .serum  +     — 9        water  is  therefore  isotonic  with  a 

solution  of  NaCl  at  °  )9-+--      -0'585  per  cent. 

Accordingly  in  calculating  the  NaCl  solution  isotonic  with  the  normal 
non-diluted  serum,  the  following  equation  may  be  employed  : — 

5: 5  +  2-85  =  0-585  :z, 

5  +  2'85xO'585 
whence  it  follows  that  :  x= —      — —       -  — O92  per  cent. 

In  this  case  the  blood  .serum  is  isotonic  with  a  NaCl  solution  of  0'92  per 
cent.  .        ' 

Raoult's  Method.- — The  determination  of  osmotic  pressure  by  this  method 
is  more  easily  carried  out.  The  apparatus  commonly  adopted  is  that  of 
Beckmann  (Fig.  43).  It  consists  essentially  of  a  glass  vessel  u,  which  is  filled 
with  a  free/ing  mixture  (crushed  ice  and  salt),  a  test-tube  B  introduced  to  a 
certain  depth  in  the  vessel  (7,  and  a  longer  tube  A  fitted  with  a  lateral  tubey 
which  also  dips  into  the  tube  B.  The  tube  A  is  closed  with  a  cork,  through 
the  centre  of  which  passes  the  special  Beckmann  thermometer  D  (or  an 
ordinary  thermometer  with  a  scale  divided  into  hundredths  of  a  degree)  and 
platinum  wire  F,  which  is  bent  into  a  loop  at  its  lower  end.  This  platinum 
wire,  which  is  intended  to  stir  the  fluid  contained  in  the  glass  tube  A,  is 
automatically  set  in  motion  by  a  little  motor  driven  by  water  or  electricity 
or  other  power.  In  using  the  apparatus  the  vessel  C  is  first  filled  with  the 
freezing  mixture,  then  a  few  c.c.  of  serum  are  poured  into  the  tube  A  till  the 
bulb  of  the  thermometer  is  covered,  when  the  stirrer  F  is  set  in  motion.  The 
mercury  column  of  the  thermometer  must  be  watched  until,  after  sinking,  it 
rises  again,  and  then  remains  for  a  few  seconds  at  the  temperature  attainedr 
which  is  the  freezing-point  of  the  liquid. 

In  practice,  it  is  usual  to  assist  the  freezing  and  rise  of  the  thermometer 
by  dropping  a  small  crystal  of  ice  into  the  liquid  through  the  lateral  tube  E. 

When  the  freezing-point,  which  Raoult  indicates  by  A  ,  has  thus  been 
obtained,  it  is  easy  in  the  case  of  blood  serum  to  calculate  the  solution  of 
'  XaCl  with  which  it  is  isotonic.  If,  &//.,  with  ox  serum,  A  =  0'55°,  when  the 
1  per  cent  solution  is  found  to  freeze  at  -  0'588°,  it  can  easily  be  calculated 
that  the  NaCl  solution  isotonic  with  the  serum  under  examination  is  equal 
to  0'90  per  cent. 

Haematocrite  Method.  —  This  method  (adopted  by  Hedin,  Gartner, 
Daland,  Koppe,  Eykman,  Gryns,  Maiica)  is  founded  on  the  property  possessed 
by  the  red  corpuscles  of  varying  their  volume  with  the  variations  of  the 
solutions  with  which  they  are  in  contact.  On  studying  the  action  of 
solutions  of  different  concentration  of  the  same  substance  (provided  there  is 
no  destructive  action  on  the  erythrocytes),  these  become  smaller  in  more  con- 
centrated solutions,  larger  in  more  dilute  solutions ;  their  volume  is  constant 
only  in  a  solution  which  is  weaker  than  that  which  crenates  the  corpuscles, 
and  stronger  than  others  which  make  them  swell  out  On  experimenting 
with  various  substances  these!  observer's  found  for  each  a  solution  at  which 


V 


THE  BLOOD:   PLASMA 


149 


the  volume  of  the  corpuscles  remains  unchanged.  These  solutions,  taken  as 
isotonic,  correspond  exactly  with  those  found  by  the  methods  of  Hamburger 
and  Raoult. 

The  apparatus  employed  is  practically  the  same  as  that  described  on  p.  104, 
Fig.  31,  save  that  the  capillary  tube  (haematocrite),  7  cm.  long,  is  divided  into 
100   parts,    finished   at   one  end    by  a    funnel- 
shaped  swelling. 

To  ascertain  the  solution  of  NaCl  that  is 
isotonic  with  that  of  mammalian  blood  serum, 
the  first  step  is  to  aspirate  into  different 
haematocrites  a  quantity  as  equal  as  possible, 
and  containing  about  0*02  c.c.  of  blood  corpuscles. 
The  haematocrites  are  placed  in  the  horizontal 
supports  represented  in  the  said  figure,  and, 
centrifuged  till  the  column  of  erythrocytes 
becomes  regular  and  constant,  while  the  height 
they  reach  is  simultaneously  noted.  Next,  to 
the  free  portion  in  each  haematocrite  is  added, 
by  means  of  a  Pravaz'  syringe  or  a  measuring 
pipette  graduated  in  hundredths  of  c.c.,  a  given 
quantity  (0'2  c.c.)  of  the  various  solutions  of 
serum,  diluted  in  the  same  way  as  those  em- 
ployed in  examination  of  the  osmotic  pressure 
of  the  serum  according  to  Hamburger's  method. 
The  erythrocytes  are  mixed  with  the  solution 
by  means  of  a  fine  needle,  care  being  taken  to 
close  the  capillary  end  of  the  haematocrite  with 
the  finger,  and  they  are  then  again  centrifuged 
for  an  hour  and  a  half,  until  the  level  of  the 
stratum  of  corpuscles  remains  constant.  This  is, 
easily  ascertained  when,  on  reading  the  height  of 
the  stratum  of  erythrocytes,  at  intervals  of  a  few 
minutes'  centrifuging,  they  show  the  same  figure. 
On  then  examining  with  a  lens  the  several 
columns  of  fluid  corpuscles,  that  solution  is  to 
be  taken  as  isotonic  in  which  the  column  in 
the  haematocrite  is  level  with  the  original. 
If  none  of  the  columns  are  exactly  in  this 
condition,  the  isotonic  solution  is  intermediate 
between  the  tube  in  which  the  corpuscles 
are  either  just  shrunk  or  just  swollen,  i.e. 
the  first  is  just  hypertonic,  the  second  is  just 
hypotonic. 

Method  of  Electrical  Conductivity.  —  The 
cryoscopic  method  enables  us  to  study  the  mole- 
cular concentration  of  the  blood  and  the  serum, 
that  of  electrical  conductivity  permits  us  to 
study  the  electrolytes  they  contain.  Accord- 
ing to  Arrhenius,  electrical  conductivity  is  due  to  the  dissociated  portion 
of  the  electrolytes,  to  the  positive  and  negative  ions  (kations  and  anions), 
their  number  and  their  velocity  in  the  fluid.  It  varies  with  everything 
that  causes  the  concentration  and  mobility  of  the  ions  to  vary,  such  as  the 
chemical  nature  of  the  electrolytes,  their  molecular  concentration,  the 
presence  of  anelectrolytes  and  colloids,  the  temperature. 

The  electrical  conductivity  (K)  of  a  solution  is  the  reciprocal  of  the 
resistance  (r),  measured  in  ohms,  which  it  offers  to  the  passage  of  the 
electrical  current. 

Resistance  is  measured  by  Kohlrausch's  method  with  the  apparatus  shown 

VOL.  I  L  & 


FIG.  43. — Beckmann's  Cryoscope. 


150 


PHYSIOLOGY 


CHAP. 


in  the  schema  of  Fig.  44.     Here  1  is  the  source  of  the  induced  current,  r  the 
resistance  of  the  liquid  to  be  determined,  R  a  resistance  expressed  in  ohms, 
T  a  telephone,  x  a  contact  that  slides  along  a  metal  wire  pq,  which  is  kept 
tense   and  parallel  with  a  scale  divided  into  1000  parts  and  one  metre  in  f* 
length. 

This  arrangement  constitutes  the  so-called  Wheatstone  Bridge,  and  no 
electrical  current  passes  through  the  telephone  T,  i.e.  it  remains  silent,  when 
the  contact  x  divides  the  wire  pq  into  two  parts,  px  and  xq,  such  that  the 
resistances  of  px,  xq,  r  and  R  are  related  thus  : — 

r  :  R  --=px  :  xq. 


FIG.  44.— Diagram  of  apparatus  used  for  determining  the  electrical  conductivity  of  fluids. 


It  is  easy  to  find  this  point  x  by  holding  the  telephone  to  the  ear  and  sliding 
the  contact  along  the  wire  pq,  the  above  ratio  enabling  us  to  calculate  the 


—,  and  noting  that  px  +  xq  =  1000  :  — 


2      « 


required  resistance,  as 


The  resistance  capacity  ((7)  of  the  cell  containing  the  fluid  to  be  examined  is 
found  by  determining  the  resistance  (2}  which  it  offers  with  a  given  solution 

of  known  conductivity  (x),  e.g.  KC1  ^  and  calculating  C=x2.     In  all  other 

fluids  to  be  examined   in  the  same  cell  the  specific  electrical  conductivity 

C 
is   calculated   on  the   basis  of  this   value,  «  =  -»-'    The  conductivity  at  25° 

of  the  serum  of  healthy  human  blood  (Viola)  calculated  in  ohms  (ccxlO6) 
oscillates  between  1128  and  1232.  That  of  the  blood  is  much  less,  and  at 
the  moment  of  clotting  it  presents  a  rapid  diminution  (Galeotti). 

Besides  osmosis  and  electrical   conductivity,  we  must  briefly 
consider  the  physiological  importance  of  another  physical  property, 


v  THE  BLOOD:   PLASMA  151 

the  viscosity  of  blood  plasma,  to  which  no  one  had  called  attention 
previous  to  the  interesting  work  of  Albanese,  On  the  Influence  of 
the  Composition  of  Nutritive  Fluids  on  the  Activity  of  the  Isolated 
Frog's  Heart  (1893). 

Let  it  be  said  in  the  first  place  that  the  viscosity  of  a  homo- 
geneous fluid,  such  as  plasma  or  blood  serum,  is  due  to  the  internal 
friction  between  its  molecules  and  those  of  the  solvent  (water), 
and  of  the  bodies  in  solution  or  in  pseudo-solution  (colloids), 
whether  or  no  these  are  electrolytes,  dissociated  or  non-dissociated  ; 
and  that  in  heterogeneous  fluids,  such  as  the  blood,  entire  or  defi- 
brinated,  the  viscosity  is  largely  augmented  by  the  presence  of  the 
corpuscular  elements. 

It  varies  considerably  with  temperature,  and  is  measured  by 
special  instruments  called  viscometers.  The  measurement  is  based 
on  the  time  which  a  known  volume  of  fluid  takes  to  pass  along  a 
capillary  tube.  When  the  pressure  under  which  the  fluid  passes, 
and  the  dimensions  of  the  capillary  tube,  are  known,  it  is  possible 
to  obtain  absolute  values  (/>)  of  viscosity  ;  but  often  it  suffices 
to  obtain  the  relative  value  (17)  by  comparison  with  that  of  another 
fluid,  e.g.  distilled  water. 

Hlirthle  suggested  another  method  by  which  it  is  possible  to 
determine  the  viscosity  of  circulating  blood  in  the  living  animal ; 
but  better  results  are  obtained  experimentally  in  vitro  and  with 
blood  serum. 

Bottazzi  found  the  value  77  at  15°  C.  for  dog's  serum  =  2-0233- 
2-0486,  and  at  39°  C.  =  1-84-1-87 ;  Mayer  at  40°  C.  for  mammalia 
obtained  values  that  oscillated  between  1*41  and  1-95.  In  the  dog 
the  viscosity  of  serum  and  defibrinated  blood  is  as  1 : 5  (Bottazzi). 

The  viscosity  of  blood  determined  by  Albanese  with  Ostwald's 
viscometer  (v.  Grundriss  der  allgemeinen  Chemie,  Leipzig,  1890)  is 
approximately  equal  to  that  of  a  2-3  per  cent  solution  of  gum 
arabic.  He  believes  in  a  certain  constant  ratio  between  isotonicity 
and  isoviscosity ;  but  this  seems  improbable,  since  the  fluids  within 
the  body  are  isotonic  but  not  isoviscous. 

The  physiological  importance  of  viscosity  depends  principally 
on  the  great  resistance  which  it  entails  on  the  blood  passing 
through  the  capillaries,  and  on  the  corresponding  effort  that  must 
be  made  by  the  heart.  But  it  is  probable  that  the  high  viscosity 
of  the  blood  and  the  presence  of  colloids  influence  some  chemical 
reactions  in  a  way  that  does  not  obtain  in  pure  water  or  in  fluids 
of  less  viscosity  ;  and  this  notwithstanding  that  the  diffusion  of 
crystalloids  in  colloid  solutions  is  effected  with  the  same  rapidity 
as  in  water.  From  this  it  appears  that  a  fluid,  in  order  to  be 
completely  physiological,  that  is  to  say,  indifferent  and  innocuous 
to  the  living  tissues,  must,  besides  being  isotonic  and  isoconductive, 
be  also  isoviscous,  i.e.  it  must  possess  a  degree  of  viscosity  equal  to 
that  of  blood  plasma. 


152  PHYSIOLOGY  CHAP. 

VIII.  In  order  to  appreciate  the  importance  of  the  functions 
of  the  blood  in  the  animal  economy,  it  will  be  well  to  examine 
briefly  the  most  important  consequences  of  haemorrhage  and 
transfusion  of  blood. 

(a)  Loss  of  blood,  however  produced,  results  in  a  weakening  of 
the  body  in  correspondence  with  the  amount  of  blood  lost.  A 
haemorrhage  of  30  grms.  is  dangerous  or  deadly  in  the  new-born 
infant,  of  180-200  grms.  in  a  child  of  one  year  old,  of  half  the  blood 
(2000-2500  grms.)  in  the  adult.  Women  appear  to  stand  loss  of 
blood  relatively  better  than  men,  because  they  have  the  power, 
being  subject  to  periodical  haemorrhages  (menstruation),  of  reform- 
ing it  more  quickly.  In  consequence  of  the  relative  speed  at 
which  blood  forms  again  it  is  possible  to  obtain  a  greater  volume 
of  blood  by  repeated  bleeding  than  was  originally  present  in  the 
animal,  without  causing  its  death. 

Vierordt  (1854)  was  one  of  the  first  to  investigate  the  effect  of 
bleeding  upon  the  number  of  red  corpuscles,  and  he  found  that 
they  diminished  continuously  with  successive  bleeding,  and .,  that 
death  occurred  when  the  relative  quantity  of  blood  corpuscles 
fell  below  a  certain  limit,  which  differs  for  different  individuals. 
If  the  loss  of  blood  is  not  pushed  so  far  as  to  kill  the  animal  there 
will  be  an  increased  influx  of  lymph  into  the  blood,  by  which  more 
water,  with  its  contained  salts  and  proteins,  is  taken  up  from  the 
tissues.  The  neo-formation  of  erythrocytes  takes  longer.  A  con- 
dition of  liydraemia  then  obtains,  associated  with  oligocythaemia 
and  leucocytosis,  due  to  the  increased  passage  into  the  blood  of  lymph 
which  carries  a  greater  number  of  leucocytes  with  it.  All  these 
facts  (and  others  which  we  shall  discuss  in  speaking  of  haemato- 
poiesis)  have  been  substantially  confirmed  by  recent  observers 
(Hayem,  Bizzozero,  Golgi). 

(6)  The  effects  of  transfusion  of  blood  are  more  important.  We 
must  distinguish  between  direct  transfusion,  from  vein  to  vein, 
and  indirect,  viz.  the  injection  of  extracted  and  defibrinated  blood, 
between  homogeneous  transfusion  of  the  blood  of  the  same  species 
and  heterogeneous  transfusion  of  the  blood  of  animals  of  other 
species. 

Direct  homogeneous  transfusion  is  readily  tolerated.  According 
to  the  observations  of  Worm-Muller  the  normal  quantity  of  serum 
in  an  animal  can  be  increased  to  83  per  cent,  in  consequence  of 
the  great  adaptability  of  the  vascular  system,  without  serious 
symptoms.  But  if  the  increase  of  blood  is  carried  too  far,  so  that 
its  quantity  is  doubled,  alarming  symptoms  occur,  and  when  the 
increase  is  raised  to  145  per  cent  the  animal  dies  from  interstitial 
haemorrhage,  in  consequence  of  vascular  laceration. 

If  a  certain  quantity  of  blood  is  transfused,  there  will  be  a 
rapid  return  to  the  normal,  owing  to  increased  elimination  from 
the  kidneys.  The  proteins  of  the  plasma  are  also  reduced  (if  less 


v  THE  BLOOD:   PLASMA  153 

rapidly)  to  the  normal  quantity,  owing  to  their  conversion  into 
nitrogenous  waste  products.  A  marked  increase  of  urea  in  urine 
is  actually  observed  during  the  first  (2-5)  days  after  transfusion 
(Worm-Miiller,  Landois).  The  erythrocytes  diminish  far  more 
slowly,  so  that  the  blood  for  about  a  month  is  richer  in  corpuscles 
(polycythaemia)  and  haemoglobin  (Panum,  Lesser,  Worm-Muller). 
The  diminution  of  the  corpuscles  is  due  to  the  breaking-up  of  their 
constituents,  as  manifested  in  a  moderate  increase  in  the*  urea 
excreted  daily  by  the  kidneys,  and  the  bile  pigments  secreted  by 
the  liver  (Landois). 

It  is  remarkable  that  a  rapid  consumption  of  transfused  blood 
is  observed  even  during  inanition.  In  a  dog  that  has  been  sub- 
jected to  a  prolonged  fast,  periodical  transfusion  does  not  hinder 
progressive  wasting  of  the  body  (Luciani). 

Indirect,  as  well  as  direct,  homogeneous  transfusion  is  tolerated 
(provided  the  amount  be  not  excessive),  although  defibrinated 
blood  contains  a  considerable  quantity  of  thrombin  and  of  co- 
agulative  nuclein- containing  substances.  Panum  succeeded  in 
replacing  almost  the  whole  of  a  dog's  blood  by  other  homogeneous, 
defibrinated  blood,  without  injury  to  the  animal.  In  this  case,  no 
plethora  is  produced ;  the  transfused  blood  is  supported  well  by 
the  new  individual,  and  shows  no  abnormal  tendency  to  degenerate. 
This  indicates  homogeneous  transfusion  as  a  rational  measure  to 
avoid  the  danger  of  death  in  severe  haemorrhage.  Since,  however, 
in  many  cases  death  ensues  not  from  deficiency  of  the  nutritive 
matters  of  the  blood,  but  because  the  necessary  mechanical  conditions 
of  the  circulation  are  wanting,  it  is  simpler  in  practice  to  replace 
transfusion  of  blood  by  intravenous  injection  of  physiological  saline 
(0'9  per  cent),  as  suggested  by  Kronecker.  The  salt  water  is  of  itself 
capable  of  maintaining  the  circulation,  giving  time  for  new  blood 
to  form,  and  thus  averting  the  danger  of  death  from  haemorrhage. 

Transfusion  of  heterogeneous  blood  is  dangerous  to  the  life  of 
the  animal  even  when  it  is  administered  in  moderate  doses.  It 
provokes  fever  with  haemoglobinuria  (Ponfik),  due  to  dissolution  of 
erythrocytes  (Landois) ;  capillary  embolism,  due  to  agglutination  of 
foreign  blood -corpuscles  (Albertoni) ;  fibrinous  clotting,  extra- 
vasation of  blood,  diarrhoea,  cholaemia,  and  bile  pigments  in  urine, 
etc.,  all  effects  of  the  destruction  of  blood-corpuscles. 

This  toxic  and  specifically  haemolytic  action  of  the  blood  of  an 
animal  in  regard  to  the  blood  of  another  animal  of  a  different 
species  is  exhibited  regularly,  but  in  varying  degrees,  in  the 
different  species.  Thus  the  blood  of  certain  fishes,  e.g.  of  the  eel 
and  lamprey,  is  excessively  toxic  to  mammals  (A.  Mosso).  In  order 
to  kill  a  rabbit,  it  suffices  to  inject  0*5  grm.  of  eel's  blood  for  each 
kgrm.  of  the  rabbit's,  into  the  circulation  or  peritoneal  cavity ;  while 
to  produce  the  same  effect  with  duck's  blood,  7  grnis.  are  required ; 
with  dog's  blood  40  grms.  per  kgrm.  (Hericourt  and  Eichet). 


154  PHYSIOLOGY  CHAP. 

The  haemolytic  or  globulicidal  toxic  action  of  heterogeneous 
blood  depends  rather  upon  the  plasma  than  on  the  blood-corpuscles. 
Approximately    the    same    effect    is    produced    by    injection    of  ' 
heterogeneous  serum  (Landois). 

(c)  The  capacity  of  the  blood,  or  serum,  to  destroy  the  foreign 
cellular  elements  that  penetrate  it,  is  intimately  connected  with 
another,  and,  from  the  medical  point  of  view,  far  more  important 
of  its  properties — viz.  destruction  of  certain  pathogenic  bacteria ; 
this  constitutes  a  natural  defence  of  the  body  against  special 
infectious  diseases,  and  is  even  more  important  than  the  phagocytosis 
attributed  to  the  leucocytes. 

Fodor  (1887)  and  then  Nuttall  and  Flugge  (1888)  were  the  first 
to  demonstrate  the  bactericidal  properties  of  the  blood  of  living 
healthy  animals.  H.  Buchner  (1889)  showed  that  these  depend  on 
the  very  unstable  proteins  of  the  plasma,  which  derive  from  the 
metabolic  activity  of  the  leucocytes  or  other  cells,  and  which  he 
designated  by  the  name  of  cdexins  (from  aAe^o-is,  defence).  He 
found  that  the  serum  lost  its  bactericidal  property  on  simple 
dialysis  with  water,  but  not  with  physiological  salt  solution. 

By  this  treatment  the  serum  only  loses  its  salts  ;  yet  after  the 
restoration  of  its  original  molecular  concentration  it  does  not 
recover  its  bactericidal  activity.  This  is  perhaps  due  to  the  fact 
that  the  salts  before  dialysis  are  in  some  way  bound  up  with  the 
proteins,  which  association,  on  account  of  its  great  instability, 
cannot  be  reinstated  when  once  disturbed  by  dialysis.  The  serum 
also  loses  its  bactericidal  effect  on  warming  to  55°  C.  for  an  hour 
or  to  52°  C.  for  six  hours,  a  fresh  proof  of  the  great  lability  of  the 
alexins. 

The  bactericidal  action  of  one  kind  of  blood  is  not  common  to 
all  other  species,  nor  does  it  extend  to  all  bacteria,  only  to  certain 
of  them.  Thus,  e.g.,  the  serum  of  human  blood  contains  alexins 
against  the  bacteria  of  typhoid  and  cholera,  while  it  has  less  effect 
upon  Staphylococcus  pyogenes,  and  none  on  streptococci  and  the 
diphtheria  bacilli  and  anthrax ;  the  serum  of  the  rabbit  and  dog 
will  kill  typhoid  bacilli,  while  the  serum  of  the  calf  and  horse 
'have  not  this  power  (Buchner)  ;  the  serum  of  the  rat  kills  anthrax 
bacilli,  while  the  serum  of  mouse,  guinea-pig,  rabbit  and  sheep  has 
no  bactericidal  effect  upon  them  (Behring). 

Yet  more  wonderful  is  the  fact,  which  has  been  recognised  for 
some  time,  that  recovery  from  certain  infectious  diseases  is  followed 
by  immunity  to  them.  Behring  and  Kitasato  (1890)  discovered 
the  cause  of  this  phenomenon  to  be  that  the  said  infections 
develop  as  an  after-effect  (in  the  blood  of  those  persons  who 
survive  them)  a  previously  non-existent  property  of  rendering 
the  bacterial  toxins  innocuous.  They  further  showed  that  if 
the  serum  of  an  individual  who  has  become  immune  to  any  given 
infection  be  injected  into  other  individuals  in  sufficient  doses, 


v  THE  BLOOD :   PLASMA  155 

it  is  capable  of  transmitting  to  those  persons  immunity  to  that 
same  disease,  to  which  they  would  previously  have  been  liable. 
These  facts  cannot  be  understood  without  admitting  that  in  such 
cases  the  infective  agent  sets  up  a  formation  of  special  protective 
substances  or  antitoxins  in  the  body,  which  are  then  poured  into 
the  blood,  and  which  apparently  consist  in  certain  special  modifica- 
tions in  the  proteins  of  the  plasma.  We  cannot,  however,  enter  at 
length  upon  this  interesting  subject  without  transgressing  the 
limits  of  a  Text-book  of  Physiology. 

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J.  MELLANBY.     The  Coagulation  of  Blood.     Journ.  of  Physiol.,  1909,  xxxviii.  28. 
J.  MELLANBY.     The   Coagulation    of    Blood,   Part    II.     The   Actions    of  Snake 

Venoms.     Journ.  of  Physiol.,  1909,  xxxviii.  441. 
H.    E.    ROAF.      The  Osmotic  Pressure    of  Haemoglobin.      Proc.     Physiol.    Soc., 

Journ.  of  Physiol.  xxxviii.  1. 


CHAPTEE  VI 

THE    CIRCULATION   OF   THE    BLOOD  :    ITS    DISCOVERY 

CONTENTS. — 1.  Physiological  necessity  for  the  circulation  of  the  blood.  Schema 
of  cardie-vascular  system.  2.  Theory  of  Galen.  3.  Discovery  of  the  lesser  cir- 
culation ^question  of  the  priority  of  Columbus,  Servetus,  and  Vesalius.  4.  Dis- 
covery of  the  general  circulation  by  Cesalpinus.  5.  Completion  of  the  work  by 
Harvey.  6.  Discovery  of  the  lymph  circulation  by  Eustachius,  Aselli,  Pecquet, 
Rudbeck,  Bartholin.  7.  Discovery  of  the  capillary  system,  and  direct  observation 
of  the  circulation  by  Malpighi.  8.  Microscopic  observations  of  the  phenomena  of 
circulation  :  Spallanzani,  Poiseuille,  R.  Wagner,  etc.  9.  Discovery  of  diapedesis 
of  blood-corpuscles  and  migration  of  leucocytes  :  Waller,  Addison,  Recklinghausen, 
Cohnheim.  Bibliography. 

THE  Blood,  in  order  to  fulfil  its  physiological  task  as  centre 
and  agent  of  the  metabolic  exchanges  of  the  whole  body, 
must  be  in  perpetual  motion  within  the  vascular  system  which 
contains  it.  If  the  blood  remained  stagnant,  that  portion  of  it 
which  lay  within  the  capillaries  of  the  pulmonary  system  might 
indeed  become  saturated  with  oxygen,  but  would  be  unable  to 
conduct  it  to  the  parts  where  it  is  required,  i.e.  to  the  parenchyma 
of  the  organs ;  on  the  other  hand,  the  portion  contained  in  the 
capillaries  of  the  aortic  system  would  become  charged  with  carbonic 
acid  which  could  not  be  exhaled  from  the  body.  The  blood  of  the 
capillaries  leading  to  the  portal  veins  would  become  charged  with 
the  nutritive  materials  taken  up  from  without,  but  would  be 
unable  to  reach  the  organs  that  require  feeding;  while  the 
products  of  consumption,  again,  would  accumulate  in  these  organs, 
since  they  could  not  reach  the  organs  of  excretion. 

I.  Owing  to  the  intensity  of  metabolism  necessary  to  the 
maintenance  of  the  principal  vital  functions,  especially  in  the 
higher  animals,  the  arrest  of  the  movements  of  the  blood  leads  in 
a  few  moments  to  death  from  asphyxia  of  all  the  tissues.  The 
vascular  system  is  therefore  provided  with  a  pumping  apparatus, 
which  serves  to  keep  the  blood  in  continuous  rapid  movement  in 
all  parts  of  the  body. 

If  we  reduce  the  cardio-vascular  system  to  a  schema  (Fig.  45), 
we  may  distinguish  anatomically  a  central  organ,  and  the  arterial, 
venous,  and  capillary  systems  :  physiologically,  a  right  or  venous, 

157 


158 


PHYSIOLOGY 


CHAP. 


and  a  left  or  arterial  heart,  connected  by  a  system  of  vessels 
running  centrifugally  and  another  running  cen  tripe  tally,  which 
are  closed,  and  communicate  by  a  capillary  system.  The  system 

of  the  lesser,  or  pulmonary,  circula- 
tion unites  the  ventricle  of  the 
right  with  the  auricle  of  the  left 
heart ;  the  system  of  the  great,  or 
aortic,  circulation  connects  the 
ventricle  of  the  left  heart  with  the 
auricle  of  the  right.  The  auri- 
culo- ventricular  orifices  and  the 
orifices  of  the  two  big  arteries 
which  arise  from  the  ventricles  are 
provided  with  valves ;  the  orifices 
of  the  great  veins,  which  open 
into  the  auricles,  have  no  valves, 
although  on  the  other  hand  valves 
are  plentiful  along  the  course  o£. 
the  veins. 

The  importance  of  the  several 
parts  of  the  circulatory  system  is 
very  different.  Only  the  capillary 
portion  serves  the  physiological 
uses  of  the  blood.  The  arteries 
and  veins  are  only  paths  to  con- 
duct the  blood  to  the  seat  of  its 
activity,  whence  it  is  again  returned 
to  the  heart.  The  heart  is  the 
motor,  a  perfect  pumping  machine 
to  circulate  the  blood,  emptying 
its  contents  into  the  arteries  during 
systole,  filling  itself  again  with 
blood  from  the  veins  during  dia- 
stole. 

The  discovery  of  the  Circula- 

uiir;   ir:iu    ii'Miii,    HI    wiittni     UI I '  •   t  M  (    'I  l.U      U1UUU         ,    •  /»       .-•  T"*l  1  J         *        1  J  1 

circulates.  Blue  indicates  the  vessels  tlOn  Ol  the  BlOOd  IS  Certainly  the 
connected  witli  the  right  heart,  in  which 
circulates  the  venous  blood.  Yellow  in- 
dicates the  lymphatic  system,  pc,  Lesser, 
or  pulmonary  circulation  ;  p,  lung ;  gc, 
great  or  systemic  circulation,  formed  by 


Fie.  4/>. — Diagram  of  cardio- vascular  system 
lied  indicates  the  vessels  connected  witl 
the  left  heart,  in  which  the  arterial  blood 


im-iv^f anf   oirnnf    va^rvrrl^rl    in 

important  event  recorded  in 

the    history   of    physiology.       By   it 
,         ,     J     ..      ,*     J  &J  „      ,     J  . 

nearly  the  whole  System  of  phySlO- 

all  the  vessels  of  the  aortic  arterial  system,    -i  i  i  JTll  1J 

and  the  venous  system  of  the  venae  cava ;    logical  and    inedlCal    knowledge,  aS 

SpCScirSm1\tOyvSS,.ce'  handed  down  from  antiquity,  re- 

ceived  a  violent  wrench,  and  under- 
went a  fundamental  reconstruction.  With  it  begins  the  modern 
science  of  physiology,  founded  on  the  ruins  of  the  ancient  doctrine. 
It  is  indispensable  that  any  one  who  aspires  to  physiological 
culture  should  be  acquainted  at  least  in  its  main  points  with  the 
history  of  this  great  discovery  (which  has  been  misrepresented  in 


vi        CIECULATION  OF  BLOOD:    ITS  DISCOVEKY      159 

many  text-books  and  monographs),  and  should  know  the  names 
of  the  men  who  have  participated  in  its  preparation  or  fulfilment. 
In  reviewing  this  interesting  history  we  shall  have  an  opportunity 
of  bringing  forward  those  fundamental  principles  relating  to  the 
Circulation,  which  must  necessarily  precede  a  more  detailed  treat- 
ment of  the  subject. 

II.  The  story  of  the  discovery  of  the  circulation  begins  with 
Galen  (125-201  A.D.),  who  in  his  vivisections  perceived  the  error 
of  the  Alexandrian  school.  Headed  by  Erasistratus  (300  B.C.), 
they  taught  that  the  left  heart  and  arteries  are  empty  of  blood, 
and  connected  with  the  small  bronchi  by  means  of  the  arteria 
aspera  (trachea),  which  serve  to  carry  the  vital  spirits  (pneuma)  to* 
the  different  parts  of  the  body,  to  animate  them ;  hence  the  veins 
alone  would  contain  the  blood  destined  to  provide  the  whole  body 
with  nutriment. 

Galen  showed  that  on  puncturing  any  artery  or  the  left  heart 
in  a  living  being,  the  blood  gushes  forth,  and,  unlike  that  of  the 
veins,  is  pure,  thin,  and  vaporous,  due,  that  is,  to  a  mixture  of 
blood  with  the  air  obtained  through  the  lungs,  "  mix  turn  quid  ex 
ambobus." 

According  to  Galen,  the  arterial  centre  is  the  left  heart,  which 
drives  the  blood  endowed  with  vital  spirits  (sang  ids  spiritosus) 
through  all  the  organs  to  invigorate  them.  The  centre  for  the 
veins,  on  the  other  hand,  is  the  liver,  from  which  the  nutritive 
blood  (sanauis  nutritious)  is  conducted  by  a  kind  of  attractive  and 
selective  force  to  every  part  of  the  body.  The  blood  of  the  right 
heart,  supplied  by  the  vena  cava  inferior,  passes  mainly  through 
the  pores  of  the  septum  (which  Galen  accepts,  although  he  declares 
them  invisible),  becomes  spirituous  by  admixture  with  the  pneuma, 
and  is  then  distributed  by  the  aorta  throughout  the  body.  A 
lesser  portion  of  the  blood  contained  in  the  right  ventricle  passes, 
however,  through  the  vena  arteriosa  (pulmonary  artery)  and  returns 
by  way  of  the  arteria  venosa  (pulmonary  vein)  to  the  left  ventricle. 

Thus  Galen  had  an  idea,  however  rudimentary,  of  the  pul- 
monary circulation,  and  knew  that  the  venous  vessels  anastomose 
with  the  arterial,  since  he  had  observed  that  an  animal  could  bleed 
to  death  from  one  artery.  One  point,  indeed,  in  his  doctrine  led 
certain  critics  astray  in  their  interpretation  of  the  text.  Galen 
assumed  that  the  blood  of  the  arteria  venosa  (pulmonary  vein) 
flowed  back  to  the  lungs  at  each  systole  (by  a  sort  of  physiological 
insufficiency  of  the  mitral  valve),  in  order  to  expel  by  expiration 
the  fuliginous  vapours  formed  in  the  blood.  He  thus  allotted  to 
the  pulmonary  vein  a  double  and  'opposite  task,  i.e.  that  of  first 
carrying  the  arterial  blood  from  the  lungs  to  the  heart,  and  then 
returning  a  portion  of  the  same  with  the  vapours  from  the  heart 
to  the  lungs.  Galen  also  assigned  a  double  function  to  the  portal 
vein,  and  assumed  that  during  digestion  it  carried  the  chyle  to  the 


160  PHYSIOLOGY  CHAP. 

liver,  and  then  when  the  intestine  was  empty  carried  the  blood 
from  the  liver  back  to  the  gut.  These  two  errors  of  the  porosity 
of  the  septum,  and  the  systolic  reflux,  have  not  a  little  weakened 
the  lustre  of  Galen's  theory  of  the  lesser  circulation]  it  cannot, 
however,  be  denied  that  he  was  the  first  to  have  any  idea  of  it,  as 
was  recognised  (long  before  G.  Oeradini  once  more  pointed  it  out) 
by  competent  interpreters,  such  as  Harvey,  Maurocordato,  Douglas, 
Haller  and  Senac,  more  particularly  on  the  strength  of  a  passage 
in  Cap.  1Q,  Book  VI.  De  usu  partium. 

Who,  then,  was  the  first  to  rectify  and  complete  the  Galenic 
doctrine,  by  denying  the  permeability  of  the  cardiac  septum,  and 
determining  that  not  merely  part,  but  the  whole  of  the  blood 
expelled  from  the  right  ventricle  returns  to  the  left  by  the 
anastomosis  of  the  pulmonary  vessels  ? 

III.  In  the  year  1553  the  Spanish  physician  and  theologian, 
Servetus,1  published  his  book  Christianismi  restitutio,  which  led, 
at  the  instigation  of  Calvin,  to  his  death  at  the  stake,  by  which 
he  perished  in  Geneva  in  the  autumn  of  the  same  year.  .  Only  two 
copies  of  this  book,  which  was  a  theological  treatise,  are  extant, 
the  greater  number  having  been  burned,  some  at  Vienna  in 
Daupliine,  with  the  author's  effigy,  and  the  rest  in  Geneva,  with  the 
author  himself.  It  contains  a  passage  in  which  Servetus  describes 
the  lesser  circulation,  denying  the  communication  between  the 
ventricles  by  the  septum,  and  affirming  that  the  blood  passes  from 
the  right  ventricle  into  the  lungs,  where  "  flavus  efficitur  et  a  vena 
arteriosa  (pulmonary  artery)  in  arteriani  venosam  (pulmonary  vein) 
transfunditur." 

In  1559,  some  six  years  later,  Realdus  Columbus  of  Cremona, 
for  fifteen  years  prosector,  and  then  successor  to  Vesalius  in  the 
Chair  of  Anatomy  at  Padua,  published  his  work  De  re  anatomica 
libri  XV.  at  Venice,  in  which  on  page  177  there  is  a  description  of 
the  lesser  circulation,  and  statement  of  the  impermeability  of  the 
septum.  The  author  lays  great  stress  upon  this  discovery,  and 
claims  priority  for  it :  "  Nam  sanguis  per  arteriosam  venam  ad 
pulmonem  fertur,  ibique  attenuatur  ;  deinde  cum  acre  una  per 
arteriam  venalern  ad  sinistrum  cordis  ventriculum  defertur  :  quod 
nemo  hactenus  aut  animadvertit,  aut  script  urn  reliquit." 

It  is  undeniable,  if  we  examine  the  date  of  the  two  publications, 
that  priority  of  discovery  belongs  to  Servetus ;  and  if  it  could  be 
proved  (as  was  attempted  by  Tollin  and  Preyer  in  Germany,  and 
by  Willis  in  England)  that  Columbus  had  read  the  Christianismi 
restitutio  of  Servetus,  the  Cremonese  anatomist  could  not  be  held 
guiltless  of  plagiarism.  Against  this  assumption,  however,  must 

1  Mosheim's  opinion  that  ''Servetus"  or  "Serveto"  was  the  anagram  of  Reves 
seems  to  be  definitely  confuted  by  Comenge,  author  of  a  memoir  La  Circulation 
de  la  sanyre  (1887),  where  it  is  proved  that  the  full  name  of  the  Spanish  doctor 
and  theologian  Avas  Michele  Servet  y  Reves,  and  that  lie  was  a  native  of  Villanueva 
di  Sinena  (Aragona),  where  his  lather  was  a  notary. 


vi        CIRCULATION  OF  BLOOD:   ITS  DISCOVEKY      161 

be  placed  certain  indisputable  facts,  which  have  been  collected  with 
great  acumen  by  G.  Ceradini  (187ti-77). 

Ceradini  points  out  that  Valverde,  a  Spanish  pupil  of  Columbus, 
ascribes  the  impermeability  of  the  septum  to  his  master  in  an 
anatomical  treatise,  which  appeared  in  Rome  in  1556.  To  this 
there  is  a  preface  dated  1554,  in  which  the  author  states  that  he 
had  already  prepared  the  numerous  plates  that  were  to  illustrate 
his  book,  which  must  have  taken  him.  at  least  twelve  months. 
This  takes  us  back  to  1553,  the  year  in  which  Servetus  published 
the  book  that  cost  him  his  life.  It  is,  further,  only  reasonable  to 
suppose  that  Columbus  had  developed  his  theory  from  his  Chair 
some  years  before  publishing  it  in  his  treatise. 

We  know  that  the  physiological  passages  of  Christianismi 
restitutio  were  first  discovered  at  the  end  of  the  seventeenth 
century.  Ceradini  shows  that  in  1571,  G-.  Giinther,  who  had 
taught  Servetus  and  Vesalius  in  Paris,  described  the  lesser  circula- 
tion in  the  words  of  Columbus,  praising  him  without  allusion  to 
his  pupil  Servetus — a  proof  that  he  was  unacquainted  with  the 
C kristianismi  restitutio.  In  all  probability  it  was  unknown  in 
Italy,  as  it  is  not  upon  the  Index  librorum  prohibitorum,  drawn 
up  by  the  Council  of  Trent,  and  published  in  Rome  by  Pius  IV. 
in  1564,  which  contains  the  two  other  heretical  works  of  Servetus, 
De  Trinitatis  erroribus. 

Lastly,  by  comparing  the  two  theories,  Ceradini  produced  cogent 
evidence  that  Columbus  was  no  plagiarist 'from  Servetus. 

Columbus  completely  and  unconditionally  denied  the  per- 
meability of  the  cardiac  septum  ;  he  affirmed  that  not  merely  the 
vena  arteriosa,  but  also  the  arteria  venosa,  were  of  a  conspicuous 
size ;  he  further  contradicted  (incorrectly)  Galen's  respiratory 
function,  that  is  the  formation  of  smoky  fumes  in  the  blood, 
and  their  expulsion  by  means  of  expiration.  Servetus,  on  the 
contrary,  while  denying  the  presence  of  openings  in  the  septum, 
admitted  that  "  aliquid  resudare  possit "  through  the  same,  and 
maintained  Galen's  doctrine  by  his  assertion  that  the  blood  "  in 
ipsa  arteria  venosa  inspirato  aere  niiscetur,  et  exspiratione  a 
fuligine  expurgatur." 

Without  going  so  far  as  to  support  Ceradini's  hypothesis  that 
Servetus  learned  the  theory  of  the  lesser  circulation  from  Columbus, 
and  attempted  to  bring  it  into  harmony  with  the  older  doctrines 
of  Galen,  we  cannot  doubt  that  the  Crenionese  anatomist  had 
expounded  his  theory  some  time  before  the  Spanish  physician  and 
theologian  published  his. 

Roth,  too,  whom  Tigerstedt  calls  the  most  learned  anatomist  of 
the  sixteenth  century,  attributes  the  discovery  of  the  pulmonary 
circulation  to  Columbus,  and  he  expressly  adds  that  there  was 
nothing  in  favour  of  the  opinion  that  Servetus  had  contributed  to 
it.  It  is  interesting  to  follow  Roth's  arguments.  He  insists  on 

VOL.  I  M       • 


162  PHYSIOLOGY  CHAP. 

the  fact  that  we  have  no  direct  means  of  estimating  the  anatomical 
knowledge  of  Servetus. 

He  had  indeed  been  dissector  for  Gltnther ;  but  the  latter  was ' ! 
a  man  of  no  originality,  and  his  Institutiones  of  the  year  1539 
showed  no  advance  on  the  1538  edition  of  the  anatomical  works 
of  Vesalius,  but  was  rather  a  retrogression. 

Another  argument  is  derived  from  analysis  of  the  anatomical 
passages  of  the  works  of  Servetus.  His  theory  of  the  oommunica- 
tions  between  the  nerves  and  vessels,  as  conjectured  by  Praxagoras, 
was  confuted  by  Galen  and  Vesalius.  '  The  impermeability  of  the 
'ventricular  cardiac  septum  belongs,  as  we  have  seen,  to  Columbus, 
and  the  capacity  of  the  pulmonary  artery  to  an  observation  of 
Vesalius.  Added  to  this,  Servetus  never  properly  verified  the  new 
anatomical  observations,  which  he  vaguely  adopted ;  and  never 
attempted  criticism  of  arguments  contrary  to  his  own  views  ;  nor 
did  he  bring  forward  any  valid  anatomical  demonstrations  in 
support  of  his  position.  From  all  this  but  cne  conclusion  is 
possible.  Servetus  worked  from  books,  and  not  from  the  subject ; 
he  was  a  compiler,  not  a  practical  anatomist. 

He  pieced  together  the  doctrine  of  Galen,  certain  ideas  of 
Praxagoras,  and  the  observations  of  Vesalius ;  with  the  discovery 
of  the  latter  he  perfected  and  completed  Galen's  rudimentary 
views  on  the  pulmonary  circulation ;  but  by  quoting  from 
Praxagoras,  he  made  a  step  backwards,  not  merely  behind 
Vesalius,  but  behind  Galen  also.  In  short,  Servetus,  animated 
by  his  desire  to  conciliate  science  with  the  Bible,  promulgated  a 
speculative,  not  a  real  anatomy,  an  anatomia  imaginabilis,  not  an 
anatomia  sensibilis. 

Roth,  therefore,  confirms  Ceradini's  statements  as  to  the 
priority  of  Columbus  over  Servetus,  in  regard  to  the  lesser 
circulation. 

It  is  interesting,  again,  to  determine  the  part  taken  in  this 
great  discovery  by  the  Belgian  Vesalius,  the  founder  of  modern 
anatomy,  to  whom  Flourens  (1857)  ascribed  priority  in  the  theory 
of  the  impermeability  of  the  septum,  while  the  theologian  Tollin 
(1884)  accused  him  of  plagiarising  from  Servetus,  an  opinion  also 
maintained  by  Tigerstedt  (1893). 

In  the  first  edition  of  his  great  work,  De  humani  corporis 
fabrica  (1543),  Vesalius  says  that  he  finds  himself  "  driven  to 
wonder  at  the  handiwork  of  the  Almighty,  by  means  of  which  the 
blood  sweats  from  the  right  into  the  left  ventricle  through 
passages  which  escape  human  vision."  In  the  second  edition 
of  this  work,  published  in  1555,  he  omits  the  expression  of 
admiration  for  the  Creator,  and  declares  himself  unable  to 
understand  how  "  per  septi  illius  substantiam  ex  dextro  ventriculo 
in  sinistram  ne  minimum  quid  sanguinis  assunii  possit."  Accord- 
ing to  Tollin,  Vesalius  must  have  derived  this  more  accurate  mode 


vi        CIRCULATION  OF  BLOOD :   ITS  DISCOVERY     163 

of  thinking   from   the  Christianismi  restitutio,  which   had   been 
published  two  years  previously,  in  1553,  by  Servetus. 

Foster,  on  the  contrary,  maintains  that  the  passage  quoted 
from  the  first  edition  of  Vesalius  was  an  expression  of  irony  on 
the  part  of  the  author,  who  frequently  made  use  of  this  means 
when  his  personal  opinions  were  in  too  forcible  contrast  with  the 
doctrine  of  Galen.  In  the  second  edition,  when  his  own  fame 
was  established,  and  the  revival  of  anatomy  had  advanced  with 
giant  strides,  he  suppressed  the  greater  portion  of  these  veiled 
doubts,  and  openly  expressed  his  own  opinions.  This  hypothesis 
of  Foster,  however,  seems  arbitrary  and  untenable,  when  we  take 
into  account  the  temperament  of  Vesalius,  and  his  critical,  not  to 
say  aggressive,  attitude  towards  the  doctrine  of  Galen,  on  account 
of  which  Silvio  gave  him  the  nickname  of  "  Vesanus." 

On  the  other  hand,  Ceradini,  by  an  elaborate  comparison  of 
the  contents  and  dates  of  some  of  the  lesser  publications  of  Vesalius 
(which  would  take  us  too  far  afield  if  we  entered  upon  it),  showed 
that  he  had  learned  the  impermeability  of  the  septum  from  his 
prosector  Columbus  at  Padua  in  1542,  and  had  defended  this 
doctrine  at  Pisa  in  1543,  without,  however,  explicitly  deducing- 
its  physiological  corollary,  the  theory  of  the  lesser  circulation, 
which  implied,  as  already  recognised  by  Galen,  an  anastomosis 
between  the  vena  arteriosa  and  the  arteria  venosa.  Vesalius 
grudged  any  praise  of  Columbus,  whom  he  never  forgave  for 
having,  as  it  seems,  excited  the  students"  of  Padua  to  animosity 
against  him. 

Without  belittling  the  great  services  rendered  by  Vesalius  in 
the  reform  of  anatomy,  it  may  be  held  proved  that  he  had  no 
direct  share  in  the  discovery  of  the  circulation.  Indirectly, 
however,  he  contributed  to  the  refutation  of  not  a  few  of  Galen's 
fallacies,  more  particularly  in  regard  to  the  theory  of  hepatic 
haematopoiesis.  The  fact  that  the  lumen  of  the  vena  cava  is 
larger  in  the  proximity  of  the  heart  than  it  is  nearer  the  liver, 
in  his  eyes  justified  the  return  to  Aristotle's  theory  of  cardiac 
haematopoiesis,  and  the  admission  that  not  only  the  arteries  but 
the  veins  also  are  dependent  on  the  heart. 

IV.  When  in  the  year  1543  Vesalius,  in  obedience  to  a  wish 
expressed  by  Cosimo  I.  dei  Medici,  who  had  appointed  him 
Professor  at  Pisa,  addressed  himself  to  giving  a  short  course  of 
"  amministrationes  anatomicae  "  upon  the  fallacies  of  Galen,  it  is 
probable  that  his  hearers  included  Andreas  Cesalpinus  of  Arezzo, 
who  was  at  that  time  barely  nineteen  years  old,  and  to  whom 
belongs  the  great  honour  of  having  first  recognised  and  demon- 
strated the  general  circulation  of  the  blood. 

In  1571  the  Aretine  physician  and  philosopher  published  his 
Peripateticarum  questionum  libri  quinque,  in  which  he  assumes 
a  constant  and  physiological  transit  of  the  blood  from  the  arteries 


164  PHYSIOLOGY  CHAR 

to  the  veins,  through  the  anastomosis,  which  he  termed  the  "  vasa 
in  capillamenta  resoluta,"  to  every  part  of  the  body ;  this  perpetual 
forward  movement  of  the  blood  from  the  vena  cavae  to  the  right' 
heart,  thence  to  the  lungs,  from  the  lungs  to  the  left  heart,  and 
from  the  left  heart  to  the  arteries  was  termed  by  him  Circulatio. 
He  was  the  first  to  recognise  the  arterial  structure  of  the 
pulsating  vessel,  which  arises  in  the  right  ventricle,  and  was 
designated  by  Galen  the  vena  arteriosa,  and  the  venous  structure 
of  the  non-pulsating  vessels,  which  had  been  known  as  the  arteria 
venosa.  He  also  recognised  that  the  blood  in  the  arteries  stands 
at  far  higher  pressure  than  that  in  the  veins,  and  that  in  its 
passage  from  the  one  to  the  other  the  capillary  anastomoses  offer 
greater  or  less  resistance  according  to  the  degree  of  their  contraction 
or  dilatation. 

Again,  in  his  books  De  plantis,  which  appeared  twelve  years 
after  the  Questiones  peripateticae,  and  would  alone  suffice  to 
bring  him  undying  fame  as  a  forerunner  of  Linnaeus,  Cesalpinus 
affirmed  that  the  blood  "  per  venas  duci  ad  cor,  et  per  arterias  in 
universum  corpus  distribui." 

In  1593  Cesalpinus  published  his  Questionum  medicarum 
libri  II.,  giving  the  experimental  evidence  for  his  theories.  He 
observed  that  when  in  a  living  animal  a  vein  was  exposed, 
ligatured,  and  soon  after  cut  below  the  ligature  in  the  direction 
of  the  capillaries,  the  blood  which  first  flowed  out  was  darker  in 
colour,  and  that  which  followed  lighter.  From  this  observation 
he  deduced  with  great  acumen  the  physiological  function  of  the 
anastomoses  that  occur  in  almost  every  organ  between  the  veins 
and  arteries,  maintaining  "  venas  cum  arteriis  adeo  copulari 
osculis,  ut,  vena  secta,  primum  exeat  sanguis  venalis  nigrior,  deinde 
succedat  arterialis  flavior,  ut  plerunique  contingit." 

He  founded  a  second  experimental  proof  of  the  circulation  on 
the  fact  that  in  any  part  of  the  body  the  ligatured  vein  swells 
between  the  ligature  and  its  capillary  origin,  and  not  between  the 
heart  and  the  ligature,  as  would  be  the  case  according  to  Galen's 
notion,  "  intercepto  enim  meatu,  non  ultra  datur  progressus ; 
tumor  igitur  venarum  citra  vinculum  debuisset  fieri." 

Notwithstanding  this  brilliant  experimental  evidence  for  the 
doctrine  of  the  circulation,  as  first  brought  forward  by  Cesalpinus, 
certain  writers,  among  them  the  celebrated  Haller,  maintained 
that  while  the  Aretine  philosopher  was  undoubtedly  acquainted 
with  the  circulation,  he  recognised  it  solely  for  the  sleeping,  and  not 
for  the  waking  state.  This  is  founded  on  a  quite  erroneous  inter- 
pretation of  a'  passage  in  which  Cesalpinus  admits  a  certain 
regurgitation  of  blood  from  the  arteries  towards  the  heart  during 
the  waking  state.  Ceradini,  with  convincing  logic,  has  shown  the 
absurdity  of  Haller's  contention,  to  be  explained  perhaps  by  the 
fact  that  as  a  member  of  the  Royal  Society  of  London  he  might 


vi        CIRCULATION  OF  BLOOD:   ITS  DISCOVEEY     165 


have  some  interest  in  debasing  the  merit  of  the  Aretine,  in  order 
to  exalt  that  of  Harvey.  It  is  unfortunate  that  Ch.  Richet,  in  his 
Dictionnaire  de  physiologic  now  in  course  of  publication,  should 
repeat  Haller's  mistake  in  regard  to  Cesalpinus,  since  it  has  been 
contradicted  by  Ceradini,  whose  historical 
studies  he  has  evidently  not  consulted. 

A  further  and  very  convincing  proof  of 
the  circulation  of  the  blood  is  the  presence 
of  the  valves,  which  occur  abundantly  along 
the  course  of  the  veins,  and  are  so  contrived 
that  only  the  centripetal  passage  of  the 
blood  is  permitted,  while  the  centrifugal  is 
impeded  (Fig.  46). 

This  evidence  was  not,  however,  adduced 
by  Cesalpinus,  for  which  he  has  been  criti- 
cised by  Sprengel,  a  medical  historian.  As 
a  matter  of  fact,  although  Cannanus  of 
Ferrara  described  certain  valves  of  the 
azygos  vein  in  1547,  and  showed  that 
their  concavity  was  directed  towards  the 
heart,  Fabricius  of  Acquapendente,  a  few 
years  later,  found  and  demonstrated  to  his 
students  analogous  valves  in  all  the  veins 
that  contribute  to  the  vena  cavae.  This 
discovery  was  first  published  in  De  venarum 
ostiolis  in  1603,  some  ten  years  after  the 
publication  of  Cesalpinus'  Questiones  peri- 
pateticae. 

On  the  other  hand,  it  must  be  stated 
that  Fabricius,  who  first  described  the 
valves  of  the  entire  venous  system,  did  not 
recognise  their  function,  which  is  to  check 
the  reflux  of  the  blood  in  a  centrifugal 

direction,  and  promote  it  in  the  centri-  FJG  46._Extenial  iliac  vein, 
petal,  by  muscular  force ;  he  assumed  that 
they  were  there  to  retard  the  current  of 
blood  from  the  heart  to  the  periphery  of 
the  veins.  Who,  then,  was  the  first  to 
establish  the  theory  of  the  circulation  upon 
the  function  of  the  venous  valves  ? 

Ceradini  deserves  much  credit  for  bring- 
ing forward  a  series  of  important  docu- 
ments, which  lead  us  to  the  logical  conclusion  that  the  first  to 
discover  the  function  of  the  valves  of  the  veins  was  the  famous 
Petrus  Paulus  Sarpi,  theologian  and  canonist  of  the  Venetian 
Republic,  the  friend  and  pupil  of  Fabricius.  It  is  a  fact 
that  some  contemporary  authors  ascribed  the  discovery  of  the 


slit  down,  and  pinned 
out  to  show  the  numerous 
valves,  in  the  shape  of 
swallows'  nests,  placed 
singly  or  'two  to  threa  to- 
gether, along  its  course. 
(Calori.)  «,  Tunica  interna, 
stripped  oft'  and  turned  over 
at  b  •  c,  valves ;  d,  tunica 
externa  ;  e,  orifices  of  branch 
veins ;  /,  branching  veins 
cut  through. 


166  PHYSIOLOGY  CHAP. 

circulation  to  Sarpi.  Frate  Micanzio,  Bartholin,  Yesling,  Gassendi, 
Walaeus,  all  hail  him  as  the  discoverer.  Yoss  (1685)  wrote  that, 
the  circulation  was  discovered  by  Cesalpinus  in  Italy,  Paulo  " 
8o/rpio  Veneto  in  primis  placuit.  Yesling  communicated  to 
Bartholin  that  after  Sarpi's  death  he  had  seen  one  of  his  autograph 
manuscripts  in  the  hands  of  the  Bros.  Micanzio,  in  which  the 
circulation  of  the  blood  was  described.  The  famous  Dutch 
physician  Walaeus  wrote  in  1640  :  "  Paulus  Servita  Yenetus  val- 
vularum  in  venis  fabricam  observavit  accuratius  ...  ex  valvularum 
coustitutione  aliisque  experimentis,  sanguinis  motum  deduxit 
egregioque  scripto  asseruit."  Unfortunately,  however,  the  manu- 
scripts of  Sarpi,  which  were  preserved  in  the  Servite  Library  at 
Yenice,  were  destroyed  by  fire,  with  a  great  portion  of  the  convent, 
in  September  1769,  only  one  fragment  from  a  letter  cited  by 
Griselini  in  his  book  Del  yenio  di  Fra  Paolo  Sarpi  (Yenice, 
1785)  remaining,  in  which  Sarpi  alludes  to  matters  by  him 
"  observed  and  described  in  regard  to  the  course  of  the  blood  in  the 
vessels  of  the  animal  body,  and  to  the  structure  and  function  of 
their  valves" 

Y.  What,  then,  was  the  real  merit  of  William  Harvey,  the 
supposed  discoverer  of  the  circulation  of  the  blood,  after  Columbus, 
after  Cesalpinus,  after  Sarpi  ?  Assuredly  lie  was  not  the  first  to 
correct  Galen's  error  as  to  the  permeability  of  the  septum,  and  to 
affirm  that  the  whole  of  the  blood  passes  from  the  right  heart  to 
the  left  through  the  pulmonary  vessels ;  this  was  the  discovery  of 
Columbus.  Nor  was  he  the  first  to  recognise  the  presence  of 
arterio- venous  anastomoses,  the  passage  of  blood  through  the  same, 
and  the  centripetal  direction  of  the  blood-stream  in  all  the- veins; 
this  was  the  great  discovery  of  Cesalpinus.  Nor,  again,  was  he 
the  first  to  describe  the  valves  of  the  veins,  for  they  were  known 
to  Cannanus,  and  were  accurately  described  by  his  pupil  Fabricius 
of  Acquapendente  ;  nor  to  discover  their  physiological  office  in  the 
circulation — this  was  the  discovery  of  Paulus  Sarpi.  Nevertheless, 
Harvey's  merit  was  immense ;  it  consisted  in  a  wider  and  stronger 
development  of  the  doctrine  communicated  by  his  predecessors,  to 
Which  he  gave  a  solid  basis  by  means  of  countless  vivisections  and 
ingenious  experiments.  He  committed  a  grave  injustice,  however, 
in  claiming  the  whole  merit  of  the  discovery,  inasmuch  as  he 
ignored  the  work,  and  omitted  to  mention  the  names,  of  Cesalpinus 
and  Sarpi. 

After  the  critical  studies  of  Ceradini  and  also  of  Tollin  (which 
coincide  in  this  matter)  it  would  be  absurd  to  pretend  that  Harvey 
was  not  fully  acquainted  with  the  works  of  Cesalpinus,  which  were 
published  in  Venice  in  1593,  some  five  years  before  Harvey  settled 
at  Padua,  where  he  remained  for  four  years  (1598-1602)  as  the 
pupil  of  Fabricius  of  Acquapendente.  His  silence,  when  accused 
of  plagiarism  by  his  contemporaries  Micanzio,  Yesling,  Walaeus, 


vi        CIRCULATION  OF  BLOOD:    ITS  DISCOVERY      167 

Riolan,  Bartholin,  and  others  indicates  that  he  prudently  avoided 
a  dispute  in  which  he  had  much  to  lose  and  nothing  to  gain. 
Willis,  in  order  to  explain  Harvey's  action,  has  recently  advanced 
the  view  that  he  was  a  freethinker,  and  anti-Trinitarian  like 
Servetus  and  Cesalpinus,  whose  works  he  certainly  knew,  and 
with  whose  views  he  fully  sympathised.  As  court  physician  to 
Charles  I.,  the  severe  persecutor  of  Anabaptists  and  anti- 
Trinitarians,  he  could  not  own  to  these  tendencies  without  grave 
danger.  Hence,  being  indisposed  to  martyrdom,  he  kept  silence. 
It  is  obvious,  however,  that  while  this  might  explain  his  attitude 
towards  Servetus,  it  could  not  apply  in  any  way  to  Cesalpinus,  who 
was  the  Pope's  chief  physician,  and  is  known  to  have  performed  the 
necropsy  of  Filippo  Neri,  in  describing  which  his  orthodoxy  is  only 
too  apparent. 

^N  evertheless,  Harvey's  little  book  of  72  pages  which  came  out 
at  Frankfurt  in  1628,  Exercitatio  anatomica  de  motu  cordis  et 
sanguinis  in  animalibus,  is  unmistakably  the  masterpiece  of  a 
man  of  genius. 

Even  now,  after  more  than  two  and  a  half  centuries  of  scientific 
discovery,  this  opuscidum  aureum,  as  Haller  termed  it,  arouses 
the  admiration  of  the  reader  by  its  lucid  ideas,  and  the  logical 
arrangement  of  its  observations,  which  were  all  founded  on  vivi- 
section. With  the  exception  of  a  few  inaccuracies  and  errors  every- 
thing it  contains  is  well  observed  and  reasoned,  and  it  may  still  serve 
as  the  introduction  to  a  deeper  study  of  this  interesting  subject. 

After  exposing  the  cardiac  region  in  the  living  animal,  Harvey 
noted  that  the  heart  is  alternately  in  a  state  of  motion  and  of  rest. 
During  systole  it  rises  and  strikes  the  thoracic  wall  with  its 
apex ;  it  contracts  in  all  its  parts,  more  particularly  in  the  lateral 
portions ;  it  hardens,  like  the  muscles  of  the  upper  arm  when  they 
contract ;  and  in  cold-blooded  animals  it  becomes  pale  when  the 
blood  is  emptied  out  of  its  cavity.  The  diastole  or  pulse  of  the 
arteries  coincides  with  the  heart's  systole.  When  the  heart  stops, 
the  arteries  cease  to  pulsate.  On  opening  an  artery  the  blood 
gushes  out  at  every  systole.  Hence  at  the  moment  of  systole  the 
blood  is  forced  into  the  arteries,  and  cannot  flow  back,  because 
the  valves  hinder  the  reflux. 

The  auricles  contract  and  relax  together  like  the  ventricles,  but 
before  them.  The  movement  appears  to  start  from  the  auricles 
and  then  reaches  the  ventricles.  When  the  heart  dies  the  left 
ventricle  is  the  first  to  stand  still,  then  follows  the  left  auricle, 
then  the  right  ventricle,  the  ultimum  moriens  being,  as  noted  by 
Galen,  the  right  auricle.  If  the  apex  of  the  heart  be  cut  when  the 
right  auricle  alone  is  contracting,  the  blood  is  seen  to  gush  out  at 
every  beat.  The  blood,  therefore,  reaches  the  ventricles  in  conse- 
quence of  the  contraction  of  the  auricles,  and  not  by  aspiration 
due  to  distension  of  the  ventricles. 


168  PHYSIOLOGY  CHAP. 

The  office  of  the  heart  in  its  movements  is  to  drive  the  blood 
from  the  veins  to  the  arteries,  and  distribute  it  throughout  the 
body.  Since  the  ventricular  septum  is  impermeable,  the  whole  of 
the  blood  must,  as  recognised  by  Columbus,  traverse  the  lungs  by 
the  arterial  vein  and  the  venous  artery,  in  order  to  pass  from  the 
right  to  the  left  ventricle.  None  of  this  is  fundamentally  new  ; 
it  is  only  the  correction  of  certain  fallacies  of  Galen  in  regard  to 
the  movements  of  the  heart. 

The  concept  of  the  general  circulation  is  expressed  clearly  by 
Harvey  in  the  following  words :  "  Patet  sanguinem  in  quodcumque 
membruni  per  arterias  ingredi,  et  per  venas  remeare ;  et  arterias 
vasa  esse  deferentia  sanguinem  a  corde,  et  venas  vasa  et  vias  esse 
regrediendi  sanguinis  ad  cor  ipsum ;  et  in  membris  et  extremitatibus 
sanguinem  (vel  per  anastomosin  immediate,  vel  mediate  per  carnis 
porositates,  vel  utroquoque  modo)  transire  ab  arteriis  in  venas; 
sicut  ante  in  corde  et  thorace  a  venis  in  arterias  ;  unde  in  circuiturn 
nioveri,  illinc  hue  et  hinc  illuc,  e  centre  in  extrema  scilicet,  et  ab 
extremis  rursus  ad  centrum,  manifestum  fit." 

To  establish  his  theories  he  gives  experimental  evidence  of  the 
three  following  propositions  : — 

1.  The  blood  expelled  by  the  contractions  of  the  heart  passes 
incessantly  from  the  vena  cava  to  the  arteries  in  such  quantity 
"  ut  ab  assumptis  suppeditari  non  possit,  et  adeo  ut  tota  inassa 
brevi  tempore  illinc  pertranseat." 

2.  The  blood  driven  forward  by  the  arterial  pulses  penetrates 
continuously  to  every  member  or  part  of  the  body,  "  majori  copia 
multo,  quam  nutrition!  necessarium  sit,  vel  tota  massa  suppeditari 
possit." 

3.  "  Ab   uno   quoque  membro,  ipsas   venas   hunc   sanguinem 
perpetuo  retroducere  ad  cordis  locum." 

The  experimental  proof  of  the  first  proposition  is  the  most 
original  part  of  Harvey's  work.  Starting  from  the  capacity  of  the 
right  ventricle  in  man  (which  contains  a  little  over  3  oz.  of  blood) 
he  pointed  out  that  a  considerable  quantity  of  blood  must  be 
driven  into  the  arteries  at  each  systole,  owing  to  the  width  of  the 
orifices  and  the  force  of  contraction.  Whatever  this  quantity,  it 
must  be  in  relation  with  the  difference  in  the  capacity  of  the  con- 
tracted and  the  dilated  ventricle.  If  the  heart  of  man  or  other 
animals  expels  only  one  dram  of  blood  in  one  contraction,  and  if  it 
contracts  a  thousand  times  in  half  an  hour,  then  in  this  short  time 
it  must  drive  ten  pounds  and  five  ounces  of  blood  into  the  arteries, 
a  quantity  far  too  large  to  be  derived  from  the  nutritive  elements 
taken  into  the  system,  unless  the  blood  returns  by  the  same  path. 
On  opening,  not  the  aorta,  but  any  small  artery,  the  whole  of  the 
blood  in  the  body  escapes  in  less  than  half  an  hour,  as  was  noted 
by  Galen. 

The  evidence  for  the  second  statement  is  merely  an  extension 


vi        CIRCULATION  OF  BLOOD :   ITS  DISCOVERY      169 

of  the  experiments  and  ideas  of  Cesalpinus.  When  the  arm  is 
tightly  ligatured,  as  for  an  amputation,  the  arterial  pulse  disappears 
at  the  periphery,  while  centrally  the  arteries  pulsate  more  strongly 
and  swell  up.  The  hand  and  arm  become  cold  after  a  time. 
When  the  arm  is  ligatured  loosely,  as  for  blood-letting,  the  arm 
swells  below  the  ligature,  and  the  veins  become  prominent  and 
varicose.  Above  the  ligature,  on  the  other  hand,  they  are  invisible. 
Tight  ligatures  impede  the  now  of  blood  through  the  arteries,  a 
loose  one  only  blocks  it  in  the  veins.  The  blood,  therefore,  passes 
from  the  arteries  into  the  veins.  In  this  Harvey,  in  slightly 


FIG.  47. — Reproduction  of  two  first  figures  in  Harvey's  work  (edition,  1(539,  ex  ojffidna  Joannis 
Maire,  Ludguni  Borfavorum).  Pig.  1  is  an  exact  imitation  of  the  figure  in  the  DC  cenarum  ostiolis 
of  Fabricius.  The  arm  is  bandaged  at  AA,  as  for  bleeding.  The  turgid  veins  are  seen,  with 
swellings  at  B,  C,  D,  E,  F,  caused  by  the  valves.  These  occur  not  merely  at  the  points  of 
bifurcation  (E,  F),  but  elsewhere  (C,  D).  Fig.  2  represents  the  same  arm,  from  which  the 
blood  has  been  expelled  by  pressure  with  the  finger  from  0  to  77.  The  vein  between  77  and  0 
is  now  obliterated,  because  at  the  point  0  there  is  a  valve,  which  prevents  the  blood  from 
flowing  back  to  77,  and  at  H  the  compression  of  the  finger  impedes  the  passage  of  the  blood  from 
the  peripheral  veins. 

different  words,  repeats  the  conclusions  of  Cesalpinus :  "  Apparet 
qua  de  causa  in  phlebotomia  .  .  .  supra  sectionem  ligamus,  non 
infra."  The  conclusion  that  the  blood  flows  to  the  several  organs 
in  much  larger  quantity  "  quam  nutritioni  sufficiens  sit,"  is  again 
taken  from  Cesalpinus,  who  described  as  "  alimentum  nutritivum  " 
what  is  brought  by  the  blood  to  nourish  the  organs,  as  "  alimentum 
auctivum"  what  returns  to  the  heart,  after  passing  from  the 
arteries  to  the  veins  by  the  capillaries. 

The  demonstration  of  the  third  point  is  founded  entirely,  on 
the  physiological  function  of  the  valves  of  the  veins.  Harvey 
treats  this  point  with  great  subtlety,  since  his  chief  concern  is  to 


170  PHYSIOLOGY  CHAP. 

convince  the  unbelieving,  and  he  gives  four  figures  of  ligatured 
arms  (one  of  which  is  an  exact  reproduction  of  the  "  Figura  I., 
Tabulae  II.  brachii  vivi  ad  sanguinis  missionein  ligati "  from  the 
treatise  of  .his  master  Fabricius,  De  venarum  ostiolis)  which 
demonstrate  the  varicose  and  congested  veins  at  points  correspond- 
ing with  the  position  of  the  valves  (Fig.  47")..  The  valves  are  not 
intended  to  hinder  the  accumulation  of  blood  in  the  lower  parts  of 
the  body,  for  they  are  found  also  in  the  jugular  veins,  which  run 
down  from  above,  in  the  renal  and  mesenteric  veins,  etc.  These 
impede  the  flow  of  blood  from  the  greater  to  the  lesser  veins,  to 
prevent  their  becoming  lacerated  and  varicose ;  they  show  that 
the  blood  in  the  veins  flows,  not  from  the  centre  to  the  extremities, 
but  from  the  extremities  to  the  centre.  Injections  from  the  greater 
to  the  lesser  veins  are  often  arrested  by  the  resistance  of  the 
valves,  while  no  difficulty  arises  in  injecting  from  the  small  to  the 
great  veins. 

If  the  blood  in  a  vein  is  compressed  with  the  linger  in  the 
ligatured  arm,  it  will  be  seen  that  the  blood  which  has  passed 
beyond  the  swelling  (formed  by  a  valve)  cannot  regurgitate,  and 
the  portion  of  the  vein  between  the  swelling  and  the  linger  seems 
to  be  obliterated.  The  function  of  the  venous  valves  is  therefore 
the  same  as  that  of  the  semilimar  valves  of  the  aorta  and  the 
vena  arteriosa  (pulmonary  artery),  which  close  the  ostiurn  and 
hinder  the  blood  from  flowing  backward. 

VI.  It  might  be  thought  that  the  Theory  of  the  Circulation  of 
the  Blood  as  demonstrated  by  Cesalpinus,  and  completed  by 
Harvey,  would  have  won  its  recognition  in  science,  and  have  been 
universally  accepted  and  adopted. 

Opponents,  however,  were  not  wanting,  among  the  most 
important  and  stiff-necked  being  Jean  Eiolan,  the  famous  Parisian 
anatomist,  and  Kaspar  Hoffmann,  a  celebrated  German  scientist  of 
the  day,  who,  like  Harvey,  had  been  a  disciple  of  Fabricius  of 
Acquapendente.  They  recognised  that  the  new  doctrine  under- 
mined the  foundations  of  the  medical  science  of  their  day,  and  all 
means  seemed  to  them  lawful  to  avert  what  they  held  to  be  a 
serious  danger.  Needless  to  say,  this  opposition  (although  it 
showed  up  certain  defects  and  fallacies  in  the  work  of  Harvey) 
only  succeeded  in  spreading  the  new  doctrine  more  widely,  and 
making  it  better  appreciated.  Ceradini's  observation  is  very  apt, 
to  the  effect  that  "  Harvey  owed  his  fame  to  the  Parisian  anatomist 
who,  after  the  death  of  Fabricius,  was  reckoned  the  first  authority 
in  Europe;  and  the  error  of  the  English  partisans  lies  in  the 
parallel  they  established  between  the  impression  produced  on 
the  scientific  world  of  his  day  by  his  writings  and  those  of 
Cesalpinus.  Had  Cesalpinus  in  his  lifetime  encountered  a  Kiolan, 
to  accuse  him  of  plagiarism,  of  absurdity,  and  of  heresy ;  had  he 
not  for  more  than  thirty  years  developed  peacefully  from  his 


vi        CIRCULATION  OF  BLOOD:   ITS  DISCOVERY     171 

professorial  chair,  first  at  Pisa  and  then  in  Home,  his  ideas  on  the 
circulation,  without  laying  stress  on  their  possible  consequences 
and  eventual  applications,  no  one  would  have  contested  with  him 
the  glory  of  the  discovery."  Harvey,  for  the  rest,  was  so  far  from 
suspecting  the  wide-reaching  consequences  of  the  theory  of  the 
circulation,  as  he  had  learned  it  from  the  Aretine,  that  it  only 
occurred  to  him  to  put  it  into  print  after  publicly  discoursing  of 
it  to  his  pupils  for  nine  years,  when  he  was  compelled  to  this 
Course  by  the  fact  that  the  doctrine  had  brought  him  on  the  one 
hand  friends  and  disciples,  on  the  other  enemies  and  opponents, 
and  that  these  last  were  making  a  mighty  disturbance.  And  even 
after  its  publication  in  1649,  the  physiological  importance  of  the 
theory  appeared  to  him  so  problematical,  that  in  his  reply  to 
Eiolan,  who  refuted  it,  because  he  saw  in  it  "  neque  efficientem, 
neque  finalem  causam,"  he  could  find  nothing  better  to  say  than 
"  Prius  in  confesso  esse  debet  quod  sit  antequam  propter  quid 
inquirendum.  .  .  .  Quod  sunt  in  physiologia,  pathologia  et 
therapeia  recepta,  quorum  causas  non  novimus,  esse  tamen  nullus 
dubitat  ? " 

Obviously,  so  long  as  the  Aristotelian  doctrine,  as  resuscitated 
by  Cesalpinus  and  Harvey,  flourished, — to  the  effect  that  the 
function  of  the  lungs  consists  in  reviving  the  blood,  and  that  these 
organs,  in  which  the  blood  becomes  once  more  spirituous  and 
subtle,  are  nourished  by  the  crude  blood  flowing  back  from  all  the 
other  organs  ;  so  long,  especially,  as  the  laboratory  for  the  blood, 
and  the  paths  by  which  the  products  of  food  digestion  reached  the 
circulation,  remained  unrecognised — for  so  long  did  the  theory  of 
the  circulation  of  the  blood  fall  short  of  its  true  significance,  and 
appear  to  be  merely  a  physiological  curiosity. 

Certain  passages  of  Galen  indicate  that  Herophilus  and 
Erasistratus,  the  heads  of  the  Alexandrian  School  (3000  B.C.), 
observed  the  chyle  vessels  in  the  mesentery  of  sheep.  At  the 
end  of  the  seventeenth  century  Portal,  and  more  than  a  century 
previously  Fracassato,  pointed  out  that  the  celebrated  Roman 
anatomist  Eustachius  (Opuscula  anatomica,  Venetiis,  1564)  in 
studying  the  course  of  the  azygos  vein  in  the  horse  had  recognised 
the  thoracic  duct,  and  even  detected  some  of  its  valves.  It  is 
certain,  however,  that  save  for  a  vague  tradition,  all  trace  of  these 
fortuitous  and  isolated  observations  had  been  lost  when  the 
Cremonese  Gaspare  Aselli,  Professor  of  Anatomy  at  Pavia,  found 
the  chyle  vessels,  which  he  termed  lacteals,  in  the  dog's  mesentery, 
in  1622.  So  fortunate  did  he  esteem  himself,  as  he  relates,  in 
having  found  what  he  was  seeking,  that  "conversus  ad  eos  qui 
aderant ;  evprjKa  inquam  cum  Archirnede."  But  he  had  no  inkling 
of  the  true  function  and  physiological  importance  of  these  vessels. 

In  the  year  1648  Pecquet,  a  young  physician  of  Dieppe,  who 
was  studying  at  Montpellier,  noted  that  the  lacteals  carried  their 


172  PHYSIOLOGY  CHAP. 

contents  not  to  the  liver,  as  had  been  supposed  by  Aselli,  but  to 
a  large  vessel  which  he  rediscovered  after  Eustachius,  the  thoracic 
duct,  which  empties  itself  into  the  subclavian  vein.  Two  years 
later,  the  lymphatics  of  the  liver  were  discovered  by  a  Swede, 
Eudbeck,  who  recognised  that  they,  too,  emptied  their  contents 
into  the  thoracic  duct.  Finally,  in  1652,  the  celebrated  Danish 
anatomist,  T.  Bartholin,  discovered  the  same  vessels  in  every  part 
of  the  body,  and  found  that  they  all  flowed,  with  the  chyliferae, 
into  the  thoracic  duct.  In  order  to  extend  the  theory  of  the 
circulation,  which  he  attributed  to  Harvey,  he  brought  out  a  new 
edition  of  his  Anatomy,  ad  sanguinis  circulationem  reformata, 
in  the  legitimate  conviction  that  he  had  found  a  new  and 
invaluable  argument,  even  though  an  indirect  one,  in  its 
favour. 

"  Eiolan,"  adds  Ceradini,  "  Eiolan  himself,  the  adherent  of 
every  old  tenet  and  opponent  of  all  that  was  new,  on  this  occasion 
held  back  the  darts  of  his  criticism,  that  he  might  not  blunt  them 
against  the  weight  of  i'acts.  Harvey  alone  rejected  chyle  as  well 
as  lymph  vessels,  together  with  the  function  of  the  thoracic  duct, 
and  died,  without  retracting  his  views,  in  1658,  six  years  after 
Bartholin." 

VII.  One  last  decisive  step  was  wanting  to  complete  the  new- 
doctrine  and  bring  it  into  prominence  —  the  discovery  of  the 
capillary  vessels  and  direct  observation  of  the  circulation  through 
these  from  the  arteries  to  the  veins.  "  Supererat,"  as  said  Haller, 
"  ut  ipsis  oculis  circuitus  sanguinis  subjiceretur." 

Galen,  as  already  stated,  was  the  first  to  postulate  a  direct 
connection  of  the  arterial  and  venous  blood  in  the  organs,  figuring 
it  as  a  direct  anastomosis  or  conjunction  of  the  two  sets  of  vessels. 
This  did  not  correspond  with  the  notion  of  Cesalpinus,  who 
certainly  admitted  that  the  communications  were  made  by  "  per 
vasa  non  desinentia,  ulterius  trasmeantia"  or  "per  vasa  in 
capillamenta  resoluta  "  (which  Harvey  translated  into  "  per  carnis 
porositates "),  thus  divining  the  existence  of  that  new  order  of 
vessels,  joining  the  arteries  with  the  veins,  which  were  subsequently 
termed  capillaries. 

Marcello  Malpighi,  in  1661,  was  the  first  to  see  the  movement 
of  the  blood  in  the  capillaries  of  the  frog's  lung  under  the  micro- 
scope. He  exclaims,  "  Talia  mihi  videre  contingit,  ut  non  im- 
merito  illud  Homeri  usurpare  possim  ad  rem  praesentem  melius  : 
magnum  certum  opus  oculis  video  "  (Fig.  48). 

After  Malpighi,  Leuwenhoek,  Cooper  and  Haller  tried  in  vain 
to  repeat  this  observation  on  warm-blooded  animals.  The  first 
who  succeeded  was  Lazzaro  Spallanzani,  who  bethought  himself  of 
using  the  hen's  egg  during  the  development  of  the  embryo.  The 
enthusiastic  words  in  which  the  great  physiologist  records  his 
discovery  are  pleasant  reading  :  "  Long  have  I  been  burning  with 


vi        CIKCULATION  OF  BLOOD :   ITS  DISCOVEEY     173 

curiosity  to  discover  the  circulation  in  warm-blooded  animals,  and 
to  grasp  it  as  completely  as  in  the  case  of  the  cold-blooded  ; 
hence  these  vessels "  (umbilicals  of  the  chick)  "  attracted  my 
observation  more  than  any  others,  and  invited  my  consideration, 
because  they  belonged  to  the  said  animals.  Since  the  room  in 
which  I  found  myself  was  insufficiently  lighted,  and  I  was 
determined  at  all  costs  to  satisfy  my  curiosity,  I  decided  to 
examine  the  egg  in  the  open,  under  direct  sunlight.  After  fixing 
it  in  the  apparatus  of  Lyonet "  (a  small  microscope  used  by 
Spallanzani)  "  I  turned  the  lens  upon  it,  and,  notwithstanding  the 
strong  light  that  surrounded  me,  was  enabled  by  focussing  my 
eyes,  to  see  plainly  how  the  blood  iiowed  in  the  entire  circuit  of 
the  arterial  and  venous  umbilical  vessels.  Thrilled  with  this 


FIG.  4s. — Holmgren's  Apparatus  (improvement  on  Malpighi's  method)  for  observing  the  pulmonary 
circulation  in  a  curarised  frog.  V,  screw  to  regulate  position  of  glass  plate,  P,  which  is  in- 
tended to  keep  the  surface  of  the  frog's  lung  flat ;  (.',  cannula'jclosed  at  the  end  by  an  elastic 
membrane,  which,  when  introduced  into  the  glottis  and  blown  up,  closes  the  opening,  so  that 
the  lung  cannot  distend.  -  u  j,^  . 

unexpected  joy,  I  felt  that  I,  too,  might  exclaim,  '  I  have  found  it ! 
I  have  found  it ! '  I  made  this  discovery  in  May  1771,  and  employed 
myself  in  the  summer  vacation  of  that  year  with  its  development." 

These  observations  of  Malpighi  and  of  Spallanzani,  a  century 
apart,  constitute  one  of  the  most  striking  incidents  in  the  history 
of  medicine ;  no  one  has  ever  contested  with  Italy  the  honour  of 
having  initiated  the  direct  observation  of  the  circulation.  Modern 
scientists,  with  more  perfect  microscopes  and  a  more  elaborate 
technique,  have  only  succeeded  in  completing  the  description  of 
the  phenomena  of  the  circulation,  as  visible  under  the  microscope. 
These  must  now  be  briefly  described,  since  they  contain  some 
interesting  data  that  should  precede  the  study  of  haemodynamics. 

VIII.  In  direct  observation  of  the  transparent  parts  of  the 
living  animal  under  the  microscope  the  blood  is  seen  to  circulate 
in  a  closed  system  of  capillary  canals,  which  unite  the  arteries  with 
the  veins  by  a  network,  and  form  a  continuous  circuit.  That  was 
the  true  discovery  of  Malpighi. 


174  PHYSIOLOGY  CHAP. 

In  all  the  vessels  a  sharp  delimitation  can  be  seen  under  the 
microscope,  in  the  form  of  two  parallel  dark  lines,  which  represent 
the  walls  of  the  vessels.  In  the  most  transparent  and  superficial 
parts,  the  structure  of  the  vessel  walls  can  also  be  made  out  to  a 
certain  extent  below  the  tissues  that  cover  them. 

The  movement  of  the  blood  within  the  vessels,  which  is  visible 
by  means  of  the  transported  corpuscles,  is  continuous,  and  is  always 
in  the  same  direction,  save  in  a  few  branches  of  the  capillary  net- 
work, in  which  a  temporary  block,  due  to  the  accumulation  of 
blood -corpuscles  or  a  transitory  reversal  of  the  current,  can 
occasionally  be  detected  (Spallanzani). 

In  certain  vessels  the  current  is  centrifugal,  that  is,  it  sets 
from  the  greater  trunks  to  the  lesser  ramifications.  In  others  it  is 
centripetal,  i.e.  from  the  lesser  ramifications  to  the  greater  trunks. 
The  former  are  evidently  arterial  vessels,  the  latter  venous. 

In  the  arteries  the  current  is  continuous,  with  rhythmical 
accelerations ;  in  the  veins  it  is  continuous  and  uniform ;  in  the 
capillary  network  it  is  irregular,  subject  to  impediments,  arrests, 
deviations,  or  accelerations,  according  as  the  blood  corpuscles  are 
dispersed  or  accumulated. 

In  the  medium  vessels,  arterial  as  well  as  venous,  a  more  rapid 
axial,  and  a  far  slower  peripheral  current  can  be  distinguished 
(Poiseuille,  1834).  The  erythrocytes  move  compactly  along  the 
axial  stream,  and  between  them  and  the  vessel  walls  on  both  sides 
a  thin  streak  of  clear  plasma  is  plainly  visible,  in  which  the  leuco- 
cytes move  at  irregular  distances  from  each  other,  ten  to  twelve 
times  slower  than  the  erythrocytes.  The  diameter  of  this  clear 
layer,  which  is  occupied  by  plasma  and  leucocytes,  and  its  relation 
to  the  diameter  of  the  axial  current,  varies  considerably  in  the 
different  vessels,  even  in  those  of  equal  cross-section. 

K.  Wagner  described  as  characteristic  of  the  blood-stream  in 
the  lungs  and  gills,  a  complete  absence  or  excessive  tenuity  of  the 
parietal  stratum,  and  lack  of  separation  between  leucocytes  and 
the  erythrocytes — the  time  required  for  such  separation  being  cut 
short,  owing  to  the  greater  current  velocity  and  less  extensive  path 
of  the  lesser  circulation. 

Poiseuille  designated  the  parietal  layer  as  the  stratum 
adhesivum,  and  considered  it  to  be  immobile  or  capable  only  of  very 
slow  motion.  From  the  theoretical  standpoint,  however,  it  is  only 
the  thinnest  stratum  of  plasma  immediately  bathing  the  internal 
walls  of  the  vessels  that  can  be  termed  immobile.  There  can  be 
no  doubt  that  the  separation  of  the  slower  peripheral  from  the  more 
rapid  axial  current  is  a  phenomenon  of  adhesion  and  of  internal 
friction  caused  by  the  viscosity  of  the  blood  plasma.  Hydrodynamic 
observations  on  the  nature  of  the  movement  of  fluids  in  tubes  have 
determined  that  the  velocity  of  motion  is  increased  for  the  axial 
portion  of  the  current,  and  decreases  gradually  from  the  central  to 


vi        CIKCULATION  OF  BLOOD:   ITS  DISCOVEKY      175 

the  peripheral  fluid  cylinders,  being  lowest  or  nil  in  those  imme- 
diately adhering  to  the  walls  of  the  tube. 

This  decrease  of  velocity  of  movement  from  axis  to  periphery 
'of  the  fluid  cylinder,  as  represented  by  the  blood,  fully  explains  the 
rotation  of  the  leucocytes  in  the  plasmatic  layer  round  an  axis 
perpendicular  to  the  direction  of  the  current.  The  necessity  of 
this  rotation  is  obvious,  when  we  consider  that  the  leucocytes 
nearest  the  axis  of  the  vessels  are  under  the  influence  of  a  more 
rapid  current  than  those  nearest  the  walls. 

The  explanation  of  the  fact  that  the  leucocytes  are  nearly 
always  in  contact  with  the  walls  of  the  vessel  while  the  erythro- 
cytes  move  along  the  axial  stream,  is  not  (as  many  think)  that 
some  viscosity  of  their  surface  makes  them  adhere  to  the  walls,  but 
lies  in  the  difference  between  their  specific  gravity  and  that  of  the 
erythrocytes.  It  can  be  demonstrated  in  the  microscope  that 
granules  of  graphite,  carmine,  and  colophonium  suspended  in 
water,  and  made  to  circulate  in  capillary  glass  tubes,  behave  like 
the  red  and  white  corpuscles  in  respect  to  parietal  and  axial 
currents.  The  granules  of  graphite,  being  specifically  heavier,  swim 
in  the  axial  current ;  the  particles  of  carmine,  which  are  specifically 
lighter,  follow  the  marginal  stream.  On  the  other  hand,  these  last 
occupy  the  axial  current,  when  they  are  made  to  circulate  with 
grains  of  colophonium,  since  the  specific  gravity  of  the  latter  is 
lower  than  that  of  carmine.  It  has  also  been  determined  experi- 
mentally that  the  leucocytes  leave  the  parietal  current  and  follow 
the  axial,  when  they  are  made  to  circulate,  not  with  erythrocytes, 
but  with  drops  of  milk,  which  are  specifically  lighter  (Funke). 

IX.  The  phenomenon  of  diapedesis  of  blood-corpuscles,  alluded 
to  in  Chap.  IV.,  which  may  be  observed  in  the  microscope,  deserves 
special  mention  on  account  of  its  great  importance. 

Cohnheim,  in  1867,  was  the  first  who  directed  the  attention  of 
biologists  to  the  fact  of  the  active  emigration  of  leucocytes  from 
the  blood-stream  through  the  uninjured  vessel  walls.  He  founded 
on  this  fact  a  new  theory  of  inflammation  and  suppuration  which 
is  a  complete  antithesis  to  that  of  his  celebrated  teacher  Virchow. 
The  same  facts,  however,  had  been  observed  and  described  in  1846 
by  Waller,  who  was  the  first  to  recognise  the  identity  of  the 
leucocytes  and  pus  corpuscles,  but  regarded  the  migration  of  the 
blood-corpuscles  as  a  phenomenon  of  filtration. 

In  1849  W.  Addison  formally  expressed  the  concept  of  an 
active  emigration  of  the  leucocytes,  and  distinguished  various 
stages  in  the  course  of  the  phenomenon. 

In  1864,  v.  Eecklinghausen  discovered  and  described  the 
movements  of  the  leucocytes  through  the  spaces  of  the  connective 
tissue  and  the  lymphatic  canaliculi  of  such  tissues  as  the  cornea, 
which  have  no  blood-vessels,  distinguishing  between  the  fixed  and 
the  movable  or  migratory  cells.  He  did  not  investigate  the  origin 


176  PHYSIOLOGY  CHAP. 

of  the  migratory  cells,  but  his  work  was  obviously  (as  stated  by 
P.  Heger)  "  the  true  introduction  to  that  associated  three  years 
later  with  the  name  of  Cohnheim." 

We  must  now  briefly  describe  the  facts  that  can  be  observed 
without  difficulty  either  in  the  mesentery  or  the  tongue  of  the 
frog,  after  it  has  been  paralysed  with  curare,  or  its  spinal  cord 
destroyed,  when  a  certain  amount  of  neuro-paralytic  dilatation  of 
the  small  arteries  is  produced. 

When  the  peritoneum  is  exposed  to  air,  the  circulation  in  the 
peritoneal  vessels  exhibits  a  marked  retardation  after  about  an 
hour,  so  that  (with  a  magnification  of  200  to  300  diameters)  the 
corpuscles  can  not  only  be  seen  distinctly  circulating  in  the 
capillaries  and  veins,  but  also  in  quicker  motion  within  the  small 
arteries. 

This   delay  has  no    sooner  begun    than  a   partial   block  and 


FIG.  49. — (Jolniheim's  apparatus  for  studying  the  course  of  the  circulatory ;  phenomena 
in  inflammation  of  frog's  peritoneum. 

accumulation  of  corpuscles  will  be  observed  in  the  capillaries, 
which  gradually  disappears  in  some  places  to  reappear  in  others. 

In  the  small  veins  the  most  conspicuous  feature  is  the  im- 
mobilisation of  the  leucocytes  on  the  internal  walls  of  the  vessels. 

As  they  leave  the  capillary  network,  they  advance  with  a  rotary 
motion  along  the  wall  of  the  vein,  and  become  fixed  in  contact  with 
those  that  are  already  immobilised.  Little  by  little  they  cover  the 
'  entire  internal  surface  of  the  small  veins,  forming  a  hollow  cylinder 
of  motionless  leucocytes  surrounding  the  cylinder  of  moving 
erythrocytes. 

On  continuing  to  observe  the  leucocytes  clinging  to  the  walls 
of  the  small  veins  and  capillaries,  it  is  possible  in  about  two  hours 
from  the  beginning  of  the  experiment  to  catch  the  corpuscles  in 
flagrante,  in  the  very  act  of  traversing  the  vessel  walls  to  penetrate 
into  the  meshes  of  the  connective  tissue  or  into  a  lymph  sheath,  or 
the  surface  of  the  serosa.  Here  and  there  on  the  outside  of  the  vessel 
an  irregular  lump  of  protoplasm  is  seen,  which  forms  a  sort  of  hernia, 
and  is  continuous  with  the  intravascular  portion  of  the  protoplasm 
of  the  corpuscles.  The  external  portion  of  the  corpuscle  becomes 


vi        CIRCULATION  OF  BLOOD:   ITS  DISCOVERY      177 

gradually  larger,  while  the  in tra vascular  portion — still  keeping 
its  round  shape — continuously  diminishes  in  volume,  till  at  last  it 
appears  only  as  a  mere  shining  point,  and  eventually  disappears 
altogether.  The  extravasated  leucocyte  is  then  seen  completely 
free  from  the  vessel ;  it  resumes  its  circular  shape,  and  remains 
motionless. 

The  direct  observation  of  diapedesis  can  be  facilitated  by  staining 
the  leucocytes  of  the  blood  with  methylene  blue  or  other  colouring 
matters  introduced  into  the  dorsal  lymph-sac  of  the  frog — the 
method  of  Cohnheim. 

Recent  researches  have  left  no  doubfc  that  the  diapedesis  of 
leucocytes  is  an  active  phenomenon,  intimately  connected  with 
their  amoeboid  mobility.  The  extravasation  of  red  corpuscles  (the 
true  haemorrhagia  pw  diapedesin,  as  divined  by  the  ancients)  is,  on 
the  contrary,  a  passive  process,  depending  either  on  rise  of  intra- 
vascular  pressure  or  on  nutritional  disturbances  and  lowered 
resistance  of  the  capillary  walls. 

In  the  frog's  peritoneum  the  extravasation  of  the  erythrocytes 
(from  the  capillaries  rather  than  from  the  veins)  is  first  noticed 
after  several  hours,  and  becomes  conspicuous  only  twenty-four 
hours  after  the  beginning  of  the  experiment,  in  the  capillary 
network  where  the  circulation  is  at  a  standstill  and  the  block  of 
corpuscles  is  greatest. 

This  observation  led  Cohnheim  to  the  opinion  that  the  leucocytes 
penetrate  through  tiny  pre-formed  stoniata  in  the  vessel  wall,  by 
which  the  erythrocytes  can  escape  only  when  the  openings  are 
abnormally  enlarged  by  the  active  work  of  the  leucocytes.  The 
opinion  that  prevails  at  present,  however,  is  that  no  pre-formed 
stomata  exist,  and  that  the  emigration  proceeds  by  temporary 
openings,  excavated  by  the  pseudopodia  of  the  leucocytes  at  the 
junction  of  the  histological  elements  of  the  venous  walls  or  capillary 
endothelia.  The  erythrocytes,  owing  to  the  softness  and  elasticity 
of,  their  protoplasm,  pass  readily  (perhaps  even  passively)  through 
the  openings  excavated  by  the  leucocytes,  as  through  a  network. 

It  is  still  doubtful  if  corpuscular  extravasation  (whether  active, 
as  for  the  leucocytes,  or  passive,  for  the  erythrocytes)  is  to  be 
regarded  as  a  physiological  phenomenon,  exaggerated  under 
abnormal  conditions  of  inflammatory  irritation,  or  as  an  emphati- 
cally pathological  phenomenon. 

E.  Hering  adopted  the  former  opinion,  on  the  strength 
of  the  following  experiment.  He  injected  a  finely  pulverised 
aniline  pigment  into  the  blood  of  an  animal,  and  after  some  time 
examined  the  hepatic  lymph,  when  he  found  numerous  leucocytes 
as  well  as  erythrocytes  impregnated  with  pigment,  but  no  free 
granules  of  pigment  in  the  lymph  plasma.  From  this  he  con- 
cluded that  under  normal  conditions  also  certain  leucocytes  (and 
possibly  erythrocytes  as  well)  migrate  from  the  vascular  system 

VOL.  I  N 


178  PHYSIOLOGY  CHAP. 

by  diapedesis,  and  penetrate  through  the  lacunae  of  the  plasma 
into  the  lymphatic  system. 

Be    this   as   it   may,  it   is   certain    that   diapedesis   proceeds  •' 
tumultuously  during  inflammatory  irritation,  and  gives  rise  to  the 
phenomenon  of  suppuration  at  the  focus  of  inflammation. 

In  order  to  complete  the  theory  of  corpuscular  diapedesis  we 
must  further  inquire  why  the  leucocytes  become  stationary  and 
adherent  at  the  origin  of  the  veins,  and  migrate  from  the  vascular 
system.  A  satisfactory  answer  to  this  question  can  only  be 
obtained  from  the  interesting  studies  of  Pfefier  on  Chemotaxis, 
which  were  alluded  to  in  Chap.  III.  (pp.  74-76). 

Leber  was  the  first  to  regard  the  migration  of  leucocytes  as 
a  chemotactic  phenomenon,  caused  by  an  attractive  or  directive 
action  exerted  by  the  chemical  products  of  the  pyogenic  or  pus- 
producing  microbes  on  the  leucocytes.  He  extracted  from  -the 
culture  of  Staphylococous  pyoyenes  aureus  a  crystallisable  substance, 
which  he  termed  phlogosiu,  and  observed  that  some  time  after  the 
introduction  of  a  capillary  tube  filled  with  a  solution  of  this 
substance  into  the  anterior  chamber  of  the  rabbit's  eye,  a  mass  of  • 
leucocytes  migrated  from  the  pericorneal  vessels. 

Lubarsch  was  able  to  show  that  living  bacteria  had  a  greater 
attraction  for  frog's  leucocytes  than  those  previously  killed  by  heat. 

Massart  and  Bordet  succeeded  in  showing  that  the  same 
leucocytes  are  attracted  by  liquid  cultures  of  different  microbes 
(v.  Fig.  19,  p.  75,  Stapliylococcus  pyogenes  albus),  by  inflammatory 
exudates,  and  by  certain  nitrogenous  or  phosphorus-containing 
waste  products,  e.g.  leucin.  They  also  discovered  another  im- 
portant fact :  if  the  leucocytes  are  narcotised  in  the  total  narcosis 
of  the  animal  by  paraldehyde  or  chloroform,  they  are  checked  like 
amoebae  in  their  active  movements,  and  all  emigration  that  might 
be  going  on  from  the  vessels  ceases  entirely.  This  confirms  the 
idea  that  the  migration  of  the  leucocytes  is  a  process  dependent  on 
their  excitability  or  amoeboid  sensibility. 

In  microscopic  observations  of  the  circulation  in  .small  vessels  and 
capillaries,  the  transparency  of  the  richly  vascular  organs  of  certain 
animals  can  be  made  use  of.  This  is  excellently  seen  in  the  frog's  lung, 
by  Holmgren's  method  (v.  Fig.  48,  p.  173).  After  cm-arising  the  animal  l>y 
the  subcutaneous  injection  of  a  few  drops  of  1  per  cent  curare  (sufficient  to 
paralyse  it)  a  lateral  incision  is  made  through  the  whole  depth  of  the 
body  wall,  a  little  below  the  anterior  limb.  The  lung  inflated  with  air 
will  usually  protrude  of  itself  from  the  opening.  To  avoid  emptying  the 
lung,  which  is  useless  for  observation  in  the  collapsed  state,  Holmgren 
employed  a  small  •cannula,  which  is  introduced  through  the  glottis,  and 
attached  by  a  ligature  to  the  lower  jaw.  The  end  of  the  cannuJa  has  two 
circular  grooves  in  which  is  tied  a  bit  of  frog's  intestine  into  which  the 
cannula  had  l>eeii  introduced.  Between  the  two  grooves  are  two  openings, 
into  which  air  is  blown  so  as  to  distend  the  intestine  drawn  over  it.  This 
dilates,  and  serves  as  a  tampon,  preventing  the  air  of  the  lung  from  escaping 
through  the  space  between  the  cannula  and  the  glottis.  A  small  rubber  tube 
is  fixed  to  the  cannula,  carrying  at  the  other  end  a  clip  which  is  closed  so 


vi        CIRCULATION  OF  BLOOD:   ITS  DISCOVEEY      179 

soon  as  the  lung  lias  readied  the  desired  state  of  extension.  To  obviate  tlie 
inconvenience  due  to  the  convex  surface  of  the  organ,  Holmgren  invented  a 
little  apparatus,  which  consists  of  a  special  frog-holder,  on  which  the  animal 
can  lie.  It  has  an  opening  closed  by  a  glass  plate,  above  which  a  second 
glass  plate  is  fixed  in  a  metal  frame,  which  can  be  raised  or  lowered  by  a 
screw.  The  lung,  suitably  inflated,  is  brought  between  these  two  plates,  its 
convex  surface  being  flattened  and  adapted  for  observation  by  gentle  pressure 
of  the  upper  plate. 

Another  admirable  subject  for  the  observation  of  the  circulation,  which 
was  used  more  particularly  by  Cohnlieim  in  his  classical  work  on  inflamma- 
tion, is  the  frog's  mesentery  (v.  Fig.  49,  p.  176).  The  experiment  is  carried  out 
as  follows  :  The  curarised  frog  is  laid  011  a  cork  plate,  with  a  hole  in  its  centre 
to  correspond  with  the  aperture  in  the  stage  of  the  microscope,  to  which  the 
cork  plate  is  fixed  by  clamps.  Above  the  hole  in  the  cork  plate  a  ring,  also 
cut  out  of  cork,  is  fixed  by  pins,  the  upper  edge  of  which  lias  a  depression 
that  serves  to  hold  the  bit  of  intestine  fixed  so  as  to  stretch  the  mesentery. 

A  lateral  incision  now  has  to  be  made  in  the  frog's  abdomen,  avoiding  the 
lateral  vein,  when  a  loop  of  intestine  is  carefully  drawn  out  with  forceps,  and 
laid  in  the  depression  of  the  cork  ring,  so  that  the  stretched  mesentery  lies 
taut  over  the  aperture  of  the  ring.  This  brings  the  part  under  examination 
to  a  higher  level  than  the  abdominal  wound,  otherwise  it  would  become 
charged  with  blood  and  serum  escaping  from  the  wound. 

The  above  ring  is  not  required  for  observing  the  circulation  in  the 
interdigital  membrane  or  tongue  of  the  frog,  or  in  the  tadpole's  tail,  etc.,  as 
these  can  be  simply  fixed  to  the  cork  plate  by  pins.  When  the  observation 
is  to  be  prolonged  for  any  length  of  time,  it  is  necessary  to  prevent  the  parts 
from  drying  up,  which  is  done  by  placing  over  them  little  strips  of  filter- 
paper  soaked  in  physiological  salt  solution.  The  same  method,  with  greater 
precautions  in  regard  to  moisture  and  temperature^  will  -Serve  for  examining 
the  capillary  circulation  in  warm-blooded  animals,  using,  '>.</.,  the  mesentery 
of  mouse,  guinea-pig,  etc. 

BIBLIOGRAPHY 

For  the  history  of  discovery  of  the  Circulation  of  the   Blood,    the    reader   is 

referred  to  the  two  following  monographs,  which  comprise  an  enormous  amount 

of  research  in  original  texts,  and  a  clear  and  impartial  criticism  of  ancient  and 

modern  contributions  to  the  literature  of  this  vexed  question  : — 

G.  CEHADINI.     Rieerche  storico-critiche  intorno  alia   scoperta   della   circulazione 

del  sangue.     Milan,  Fratilli/Richiedei,    3876    (333    pp.).      Difesa  della   mia 

Memoria  intorno  alia  scoperta  della  circula/done  del  sangue,  contro  1'  assalto 

dei  signori  H.  Tollin  teologo  in   Magdeburg,  e  W.   Preyer  lisiologo  in  lena. 

Con  qualche  nuovo  appunto  circa  la  storia  della  scoperta  medesima.     Genoa, 

1876. 

SlB  MICHAEL  FOSTEK.     History  of  Physiology.     Cambridge,  1901. 
R.  WILLIS.     Preface  to  Sydenliain  Edition  of  Harvey's  Works.     London,  1878. 
M.  ROTH.     Andreas  Vesalius  Bruxelliensis.     Berlin,  1902. 

For  discovery  of  Lymph  Circulation  the  tine  article  in  Lipsius  may  be 
consulted  : — 

W.  His.  Uber  die  Entdeckuiig  des  Lymphsystems.  Zeitschr.  f.  Anat.  u. 
Entwickelungsgeschichte,  1875. 

For  discovery  of  Corpuscular  Diapedesi.s,  a  complete  account  will  be  found  in 
the  following  memoir  : — 

P.  HEGER.  Etude  critique  et  exp.  sur  I'enrigration  des  globules  de  sang, 
envisagee  dans  ses  rapports  avec  I'inflammation.  Brussels,  H.  Mauceaux, 
1878  (116  pp.). 

For  Phagocytosis  and  Chemotropism  of  Leucocytes  see  : — 

E.  METSCHNIKOW.  Leoons  sur  la  pathologic  comparee  de  I'inflammation.  Paris, 
1892. 


CHAPTEE  VII 

MECHANICS    OF   THE   HEART 

CONTENTS.  —  1.  Description  of  cardiac  cycle  or  revolution.  2.  Changes  of  ex- 
ternal form,  of  the  internal  cavity,  of  the  position  and  volume  of  the  heart  in  the 
different  phases  of  its  activity.  3.  Mechanism  of  semilunar  valves.  4.  Mechanism 
of  auriculo- ventricular  valves.  5.  Theory  of  so-called  heart-sounds.  6.  Variations 
of  pressure  within  the  auricles  and  ventricles  during  the  cardiac  cycle.  7.  The 
diastolic  aspiration  ;  various  explanatory  hypotheses.  8.  Cardiac  plethysniograms  ; 
theory  of  active  diastole.  9.  Cardiograms  ;  theory  of  heart-beats  or  impulses. 
10.  Other  mechanical  effects  of  cardiac  activity.  11.  Work  done  by  the  heart. 
Bibliography. 

THE  continuous  circulation  of  the  blood  from  the  arteries  to  the 
veins  through  the  capillaries  demands,  as  its  first  indispensable 
condition,  a  mechanism  by  means  of  which  blood  pressure  is 
maintained  high  in  the  arteries  and  low  in  the  veins,  so  that  there 
is  a  considerable  difference  of  pressure  between  the  two  parts 
of  the  vascular  system.  This  mechanism  is  represented  by  the 
heart,  which  in  its  rhythmical  movements  drives  as  much  blood 
through  the  aorta  and  pulmonary  artery  during  systole,  as  it 
receives  from  the  venae  cavae  and  pulmonary  veins  during  diastole. 

I.  When  the  movements  of  the  exposed  heart  are  observed  in 
the  living  animal,  a  series  of  phenomena,  which  are  repeated  at 
regular  intervals,  is  witnessed.  Each  such  cycle  of  movements  is 
known  as  the  cardiac  cycle,  or  revolution.  The  duration  of  each 
cycle  is  exactly  equal  to  the  time  interval  between  any  two 
recognisable  arterial  pulses. 

This  interval  may  be  divided  into  three  periods :  in  the  first 
is  the  (normally  synchronous)  systole  of  the  two  auricles ;  in  the 
second,  the  (normally  synchronous)  systole  of  the  two  ventricles ; 
in  the  third,  the  pause  or  rest  of  the  whole  heart.  For  simplicity's 
sake,  the  first  may  be  termed  pre-systole  ;  the  second,  systole  ;  the 
third,  peri-systole.  The  diastole  of  the  auricles  coincides  with  the 
commencement  of  systole,  the  diastole  of  the  ventricles  with  the 
commencement  of  perisystole. 

The  words  awToK-fj  and  diao-roXr/  from  <ru-a-T^\\€iVj  contrahere,  and  5ia-<TTt\\eiv, 
distrahere,  were  first  used  by  Galen.  The  term  peri-systole  for  the  resting' 
period  of  the  heart  as  a  whole  was  introduced  by  Riolan  (Encheiridium 

180 


CHAP.  VII 


MECHANICS  OF  THE  HEAET 


181 


anatomicum,  1649),  that  of  pit-systole  by  Spring,  1860,  who,  however,  intended 
to  describe  an  imaginary  active  dilatation  of  the  ventricle,  immediately 
preceding  systole. 

Normally  the  duration  of  presystole  is  much  shorter  than 
that  of  systole.  With  accelerated  cardiac  rhythm,  i.e.  when  the 
period  of  the  cardiac  cycle  decreases,  perisy'stole,  more  particularly, 
shortens,  and  shows  a  tendency  to  disappear  altogether ;  the 
duration  of  systole,  on  the  other  hand,  is  either  unchanged 
(•Ludwig),  or  shortens  only 
when  there  is  an  exag- 
gerated acceleration  of 
rhythm  (Donders). 

Presystole  consists  in  a 
contraction  of  the  mus- 
cular walls  of  the  auricles, 
seen  with  the  unaided  eye 
to  be  peristaltic ;  this  peri- 
stalsis starts  from  the 
extreme  end  of  the  veins 
which  open  into  the  aur- 
icle, is  propagated  in  the 
auricle  from  above  down- 
wards, and  extends  as  far 
as  the  auriculo- ventricular 
groove.  The  presystolic 
contraction  diminishes  the 
cavity  of  the  auricles  in 
every  diameter,  least,  how- 
ever, in  the  longitudinal 
direction  (Kiirschner). 

The  striated  muscle 
fibres  with  which  the 
veins  are  provided  in  the 
vicinity  of  their  openings 
into  the  auricle,  and  the 
arrangement  of  the  mus- 
cular fibres  of  which  the 
walls  of  the  auricles  con- 
sist (Figs.  50,  51),  account  for  the  changes  in  diameter  exhibited 
in  presystole. 

In  systole,  the  ventricles  seem  on  simple  inspection  to  contract 
simultaneously  at  every  point.  Yet  more  delicate  observation 
shows  that  the  contraction  here  also  is  peristaltic,  commencing  at 
the  auriculo-ventricular  groove,  when  the  presystolic  movement 
has  reached  its  maximum,  and  spreading  thence  to  the  apex  with 
such  velocity  that  the  eye  cannot  follow  it.  Systole  is  accordingly 
only  a  continuation  of  the  presystolic  contraction  wave,  which 


FIG.  50. — Human  heart  dissected  after  boiling,  to  show 
superficial  muscular  libres,  seen  anteriorly.  (Allen 
Thomson.)  a',  Aorta ;  b',  pulmonary  artery  cut  short 
close  to  semi  lunar  valves,  to  show  anterior  fibres  of 
auricles  ;  a,  superficial  layer  of  fibres  of  right  ventricle  ; 
b,  that  of  left ;  c,  c,  anterior  interventricular  groove  ;  <t, 
right  auricle ;  <l',  its  appendix,  both  showing  chiefly 
perpendicular  fibres  ;  e,  upper  part  of  left  auricle ; 
between  e  and  b'  the  transverse  fibres,  which,  behind 
the  aorta,  pass  across  both  auricles  ;  e',  appendix  of 
left  auricle  ;  /,  superior  vena  cava  round  which,  near 
the  auricle,  circular  fibres  aro  seen  ;  g,  g',  right  and  left 
pulmonary  veins  with  circular  bands  of  fibres  surround- 
ing them 


182 


PHYSIOLOGY 


CHAP. 


suffers  a  brief  delay  on  reaching  the  auriculo-ventricular  groove, 
and  is  then  propagated  with  extreme  rapidity  from  base  to  apex 
of  the  ventricles. 

It.  The  changes  exhibited  in  the  three  principal  diameters  of 
the  ventricles,  and  the  modifications  of  the  internal  conformation 
of  the  heart  during  systole,  can  be  estimated  by  direct  observation 
(Harvey),  by  approximate  measurements  (Ludwig),and  by  recording 
apparatus  (Roy  and  Adaini).  Not  only  the  transverse  diameter— 
which  no  one  contests — but  the  longitudinal  diameter  also,  shorten 

during  systole  ;  the  sagit- 
tal or  antero  -  posterior 
diameter  seems  on  the 
other  hand  to  lengthen 
a  little  —  although  this 
is  contradicted  by  some 
observers.  It  is  certain 
that  during  systole  the 
elliptical  base  of  the 
heart  becomes  almost 
circular,  and  the  apex, 
which  in  rest  is  tilted  to 
the  left,  becomes  perpen- 
dicular to  the  centre  of 
the  base,  advancing  to- 
wards the  thoracic  wall. 
The  ventricles  simul- 
taneously undergo  a 
twist  from  left  to  right, 
by  which  a  portion  of 
the  left  ventricle  wall 
becomes  visible,  which 

FIG.  51.— Posterior  view  of  same  preparation  as  in  preced-    during  rest  is  COVCred  by 

the  wall  of  the  left  lung. 
That  these  changes 
of  form  in  the  ventricles 
during  systole  depend 
essentially,  like  those  of 
the  auricles  during  presystole,  upon  the  specific  structure  of  the 
myocardium,  is  shown  by  the  fact  that  the  same  changes  of  form 
and  diameter  can  be  observed  in  the  mammalian  heart,  when 
excised  and  placed  upon  a  flat  surface  (Ludwig). 

The  structure  of  the  myocardium  is  so  complicated  that  it 
only  lends  itself  to  schematic  representation,  and  not  to  exact 
description.  The  more  recent  studies  of  Hesse  and  Krehl,  follow- 
ing on  those  of  Ludwig  and  Henle,  have,  however,  cleared  up  the 
points  of  greatest  physiological  interest,  which  may  now  be  briefly 
summarised. 


ing  figure.  (Allen  Thomson.)  a,  Left  ventricle  ;"  It,  left 
ventricle  ;  <;  <•',  posterior  interventricular  groove  ;  il,  right 
auricle ;  c,  left  auricle ;  /,  superior  vena  cava ;  g,  g', 
pulmonary  veins  cut  short ;  h,  sinus  of  great  coronary 
vein  covered  by  muscular  fibres ;  //',  middle  cardiac- 
vein  .joining  coronary  sinus  ;  i,  infer.or  vena  cava  ;  i', 
Eustachian  valve. 


VII 


MECHANICS  OF  THE  HEART 


183 


The  external  muscular  layer  of  the  myocardium  is  common 
to  both  ventricles 
(Figs.  50,  51,  52). 
Its  fibres  take  origin 
in  the  fibrous  ring 
at  the  base  of  the 
ventricle ;  they  de- 
scend obliquely  from 
above  downwards, 
and  after  rejoining 
the  apex  of  the 
heart  most  of  them 
form  a  vortex,  sink- 
ing deeper  and  fur- 
nishing almost  the 
whole  of  the  inner 
layer  of  the  left 
ventricle,  papillary 
muscles,  columnae 
carneae  and  muscu- 
lar fascia  oi  the  FIG.  52.— Surface  tlbres  of  ventricles  of  human  heart  from  the  front 
nVinrrlna  fori  and  below.  (Reid.)  a.  Vortex  of  apex';  i>,  bundle  of  fibres  emerg- 

ing from  exterior  of  left  ventricle  at  vortex  a,  and  crossing  lower 

Of  the  mitral          I)art  of  septum  uninterruptedly.     At  d  the  surface  fibres  are 
,  „  somewhat  interrupted. 

valves,  as   first   de- 
scribed by  Oehl.     The  fibres  of  the  internal  muscular  layer  of  the 

right  ventricle,  on  the 
contrary,  originate  in 
the  upper  border  of  the 
interventricular  sep- 
tum, and  form  numer- 
ous reticulated,  almost 
transverse,  trabeculae. 
At  different  heights  of 
the  ventricular  cavity, 
innumerable  little 
muscle  bundles  and 
tendon  fibres  unite  the 
septum  with  the  walls 
of  the  ventricle,  while 

Fio.  53.— Section  across  middle  third  of  a  human  heart  fixed  Other  Separate  bundles 
in  diastole.  Seen  in  perspective.  (Krehl.)  The  cavity  of  oGPf>nrl  p«  ™millnrv 
the  right  ventricle  shows  a  number  of  trabeculae,  muscle  dbCeilU  <*b  d,iy 

muscles,  to  unite  by 
the  chordae  tendineae 
with  the  tricuspid  valve 
(Fig.  53). 

In  the  cavity,  both  of  the  left  and  of  the  right  ventricle,  two 
parts  of  the  internal  wall  can  be  distinguished,  which  are  termed 


bundles  and  tendinous  filaments,  which  connect  the  walh 
of  the  ventricle  in  every  direction  with  the  interventricular 
septum.  The  cavity  of  the  left  ventricle  is  much  simpler. 
The  figure  a4so  gives  a  clear  idea  of  the  difference  in  thick- 
ness of  the  walls  of  the  two  ventricles. 


184 


PHYSIOLOGY 


CHAP. 


COD!  arteriosi  (lying  beneath  the  orifices  of  the  aorta  and  pulmonary 
arteries);  these  present  a  smooth  surface,  destitute  of  reticular 
trabeculae,  and  provided  with  stout  bundles  of  longitudinal 
muscles. 

The  far  greater  bulk  of  the  walls  of  the  left  ventricle,  in 
comparison  with  those  of  the  right,  is  especially  due  to  the 
presence  of  a  third  layer  of  muscle  fibres,  which  can  be  isolated 
with  nitric  acid;  this  dissolves  the  tendinous  and  connective 
tissues,  making  it  possible  to  separate  the  inner  and  outer  coats  of 
muscle  fibres.  In  this  way  an  intermediate  layer  of  fibres  can  be 
isolated  which  are  almost  circular  in  direction  and  form  a  some- 
what conical  mass ;  these  do  not  end  in  tendons,  but  wind  round 

upon  themselves,  and  belong  ex- 
clusively to  the  left  ventricle 
(Krehl :  Fig.  54). 

No  less  interesting  than  the 
changes  of  external  form  are  the 
systolic  changes  within- the  ven- 
tricular cavities.  To  form  an 
adequate  notion  of  these,  it  is 
necessary  to  fix  and  harden  two 
human  hearts,  one  in  a  state  of 
total  systole,  the  other,  as  nearly 
as  possible  of  the  same  size,  in  a 
state  of  maximum  diastole  (Krehl's 

Fi«s.   ;-,4.— Middle    layer   of   muscular    fibres,    metftOCl> 
destitute  of  tendons,  from  left  ventricle  of 

human  heart,  after  removing  internal  and  Io  obtain   the   dead    heart   fixed    111 

external  layers.    The  form  of  the  heart  is    diastole,  it  must  either  not  have  entered 
schematically    indicated.      J    the   natural      •,  ,.     •  . .  L    i  '    j 

size.   (Krehl.)  the  state  ol  ngor  mortis,  or  must  already 

have  passed  out  of  it.     After  carefully 

removing  the  heart  from  the  thorax,  all  the  great  vessels  must  be  made 
water-tight  (by  means  of  corks  introduced  into  their  lumen),  with  the  excep- 
tion of  the  pulmonary  vein  and  the  vena  eava  superior,  into  which  two 
glass  tubes  of  the  same  calibre  as  that  of  the  vessels  must  be  introduced,  and 
fixed  by  ligatures.  Through  these  tubes  the  heart  is  filled  with  water  under 
a  hydrostatic  pressure  of  50-100  mm.  of  mercury.  The  water  enters  by  the 
'great  veins  into  the  auricles,  and  by  the  aorta  into  the  coronary  arteries,  out 
of  which  it  filters  slowly  through  the  cai-diac  walls.  The  heart  is  thus 
thrown  into  acute  diastole,  which  is  more  pronounced  than  in  life,  and 
is  left  6-8  hours  in  this  state.  It  is  then  fixed  with  96  per  cent  alcohol, 
which  is  passed  through  it  for  3  to  4  hours  under  the  same  pressure  as  that 
used  for  the  water.  To  complete  the  hardening,  absolute  is  substituted  for 
the  dilute  alcohol,  without  any  further  pressure. 

Fixation  in  systole  is  effected  by  Hesse's  heat  method.  The  freshly 
extracted  heart  is  placed  for  an  hour  in  a  solution  of  potassium  bichromate 
at  52°  C.,  which  throws  it  into  a  state  of  pronounced  systole. 

Total  systole  of  the  human  heart  can  only  be  demonstrated  on  the  heart 
of  a  subject  who  has  died  suddenly,  at  the  maximum  of  rigor  mortis. 

Dissociation  of  the  cardiac  fibres  is  easy  after  treatment  with  ordinary 
nitric  acid.  This  acid,  however,  shortens  the  muscle  fibres,  and  throws  the 
heart  into  more  or  less  complete  systole.  In  order  to  dissect  out  the  heart 


VII 


MECHANICS  OF  THE  HEAET 


185 


in  diastole,  it  is  necessary  to  prepare  it  with  the  acid  under  a  pressure  of 
60  nun.  mercury.  This  may  be  a  complete  success,  but  often  fails,  owing  to 
the  easy  rupture  of  the  heart,  more  particularly  of  the  auricles.  After 
submitting  it  to  the  action  of  the  acid  for  about  three  hours,  the  heart  is  laid 
for  several  days  in  water,  in  which  the  connective  tissue,  softened  by  the 
acid,  partly  dissolves,  and  the  rest  can  be  readily  separated  from  the  muscular 
tissue.  The  muscle  fibres  can  then  be  teased  out  without  difficulty. 


FIG.  55.— A,  Section  tli  rough  heart  of  a  criminal,  fixed  in  systole,  at  limit  of  lower  third  of  ventricles. 
A',  Section  through  same  heart,  Ht  limit  of  upper  third.  B,  Section  through  heart  of  approxi- 
mately the  same  size  as  the  preceding,  tixed  in  diastole,  at  same  level  as  A.  JJ',  Section  of 
same  heart,  at  level  of  A'.  All  four  figures  are  diminished  by  half.  (Krehl.) 

The  cavity  of  the  left  ventricle,  seen  in  section,  appears  in 
systole  as  an  irregular,  somewhat  star-shaped  fissure,  the  centre  of 
which  corresponds  with  the  conus  arteriosus.  This  proves  that 
the  left  -ventricle  is  unable  to  empty  itself  completely,  even  in 
maximal  contraction,  so  that  a  small  quantity  of  blood  is  left  in 
it,  more  especially  in  the  space  immediately  behind  the  semilunar 
valves  of .  the  aorta.  Its  driving  power  depends  mainly  on  the 
middle  layer,  contraction  of  which  must  produce  a  lengthening 
of  the  longitudinal  diameter  of  the  ventricle  :  this  is,  however, 


186  PHYSIOLOGY  CHAP. 

checked  by  the  contraction  of  the  external  and  internal  coats, 
which  compress  the  middle  coat  from  above  downwards.  The 
longitudinal  diameter  of  the  left  ventricle  thus  remains  almost 
unaltered  (Krehl). 

The  cavity  of  the  right  ventricle  is  reduced  in  the  maximal 
systole  to  a  narrow  space,  which  is  curved  towards  the  left  ventricle 
on  account  of  the  convexity  of  the  septum  (Fig.  55).  O\ving  to 
the  absence  of  a  middle  layer,  the  longitudinal  diameter  of  the 
right  ventricle  is  bound  to  shorten,  and  contributes  to  the  conical 
shape  assumed  by  the  heart,  the  apex  becoming  almost  ventrical 
to  the  centre  of  the  base.  The  numerous  trabeculae  with  which 
the  inner  layer  of  the  right  ventricle  is  provided,  and  which 
connect  its  walls  with  the  septum,  must  help  to  bring  ventricle 
and  septum  together,  and  produce  an  almost  complete  occlusion  of 
the  cavity. 

Besides  changes  of  form  we  have  to  consider  those  of  position 
and  volume,  which  are  brought  about  in  systole. 

It  is  easy  to  see  by  direct  observation  of  the  exposed  living 
heart  that  the  systolic  shortening  of  its  longitudinal  diameter 
occurs  not  by  lifting  the  apex,  but  by  dropping  the  base.  Hay  craft 
(1891)  demonstrated  this  on  the  closed  thorax  of  cat  and  rabbit  by 
pushing  needles  into  the  heart,  which  acted  as  levers,  their  fulcrum 
being  in  the  wall  of  the  thorax.  The  end  of  the  needle  fixed  in 
the  base  of  the  heart  oscillated  upwards  at  each  systole,  showing 
that  the  base  in  which  it  was  plunged  had  sunk.  The  needles 
fixed  lower  down  oscillated  in  a  less  degree.  Lastly,  if  pushed 
into  the  apex,  the  needle  trembled  but  slightly,  showing  this  to  be 
the  point  that  undergoes  least  shifting  in  systole  from  above  down- 
wards, so  that  the  shortening  of  the  long  diameter  (which,  as  we 
have  shown,  is  due  to  the  longitudinal  fibres  of  the  right  ventricle) 
is  practically  compensated  by  the  downward  movement  of  the 
base. 

The  apex,  however,  presses  a  little  on  the  thoracic  wall,  either 
because  the  heart  assumes  a  conical  shape,  or  because  the  base 
not  only  sinks  during  the  emptying  of  the  ventricle  but  is  also 
tilted  a  little  more  obliquely  from  the  back  forwards  (Carlile  and 
Ludwig). 

Along  with  the  mechanical  effects  of  the  cardiac  cycle  it  is 
necessary,  lastly,  to  consider  the  changes  of  volume  produced  in 
the  heart  during  this  revolution.  From  what  has  already  been 
said  it  is  evident  that  the  volume  of  the  heart  diminishes  during 
systolic  evacuation,  and  increases  during  perisystolic  filling.  It 
is  further  apparent  that  the  state  of  maximum  evacuation  and 
minimum  volume  (which  Ceradini  proposes  to  call  meiocardia) 
coincides  with  the  termination  of  systole,  and  that  the  moment  of 
maximal  filling  and  maximal  volume  (auxocardia)  coincides  with 
the  close  of  perisystole. 


vii  MECHANICS  OF  THE  HEAET  187 

III.  The  active  mechanical  functions  of  the  cardiac  muscles 
are  intimately  connected  with  the  passive  mechanical  functions  of 
the  semilunar  and  intracardiac  valves,  with  which  the  arterial  and 
auriculo-ventricular  orifices  are  respectively  provided. 

The  semilunar  valves  are  fibrous  membranes,  forming  pockets 
attached  to  the  edges  of  the  arterial  orifices,  their  concavity  being 
turned  upwards,  and  their  curved  free  borders  nearly  always 
provided  with  a  nodule  (corpus  Arantii).  These  valves  are  regularly 
arranged  so  that  one  segment  corresponds  with  the  posterior  wall 
of  the  aorta,  and  one  with  the  anterior  wall  of  the  pulmonary 
artery  :  the  remaining  two  closing  with  the  former  and  converging 

v     '  O  O  O 

towards  the  anterior  wall  of  the  aorta,  and  the  posterior  wall  of 
the  pulmonary  artery. 

Each  segment  at  the  place  where  it  is  attached  to  the  arterial 
orifice  abuts  on  a  dilatation  in  the  artery,  which  is  known  as  the 
sinus  Valsalvae. 

Above  the  three  reunited  sinuses  is  the  dilatation  of  the  first 
section  of  the  two  arteries,  which  is  known  as  the  bulbus 
arteriosus.  The  aorta  accordingly  possesses  one  posterior  and  two 
anterior  lateral  sinuses,  a  right  and  a  left ;  from  each  of  these 
arises  a  coronary  artery,  right  and  left.  In  the  pulmonary  artery 
we  have,  on  the  contrary,  one  anterior  and  two  posterior  sinuses, 
from  which  no  arteries  arise. 

Acquaintance  with  the  anatomical  form  of  these  valves  suffices 
to  show  that  their  physiological  function  can  be  no  other  than  to 
inhibit  or  moderate  the  reflux  of  blood  from  the  arteries  to  the 
ventricles  in  diastole,  while  they  readily  permit  the  efflux  from 
ventricles  to  arteries  during  systole.  From  Galen  to  Vesalius,  and 
from  Vesalius  to  our  own  day,  it  has  been  held  that  the  opening  of 
the  semilunar  valves  was  the  effect  of  the  torrent  of  blood  rushing 
from  the  ventricles  at  systole,  and  that  their  closing  was  due  to 
the  regurgitatioii  of  blood  from  the  artery  to  the  ventricle  at  the 
commencement  of  diastole  :  "  nam  obstaculum  ne  quid  penitus 
regurgitaret  effingere  fuit  impossibile  "  (Vesalius).  Supposing  that  in 
systole  the  semilunar  valves  are  completely  raised,  so  that  they  are 
applied  to  the  walls  of  the  sinus  Valsalvae  and  occlude  the  openings 
of  the  coronary  arteries  (Thebesius,  Brlicke),  or  that  they  assume 
the  half-open  position  (Hamburger,  Elidinger,  Hyrtl),  then  at  the 
beginning  of  diastole  a  greater  or  less  reflux  of  blood  must  be 
postulated,  to  bring  the  valves  back  from  the  open,  or  half-open, 
position  to  that  of  complete  closure.  Ceradini  (1871)  was  the  first 
who  demonstrated  that  the  office  of  the  semilunar  valves  was  not 
to  moderate,  but  entirely  to  inhibit  .the  diastolic  reflux. 

He  repeated  and  perfected  certain  experiments  of  llildinger  in 
direct  observation  of  the  valves,  by  applying  a  sort  of  speculum 
cordis  to  the  cadaveric  heart,  while  imitating  the  cardiac  systole 
and  diastole,  and  was  able  to  show  : — 


188  PHYSIOLOGY  CHAP. 

1.  That  the  position  of  elastic  equilibrium  of  the  semilunar 
valves    corresponds    not    with    closure   but   with    half -opening 
(Fig.  56). 

2.  That  during  the  systolic  efflux  the  three  sinuses  of  Valsalva 
and  the  bulbus  arteriosus  dilate,  and  the  semilunars  assume  and 
maintain    a   half-opened   position,  with   vibration    of  their    free 
borders,  which  therefore  become  blurred  and  give  rise  to  a  muffled 
sound. 

3.  That  at  the  cessation  of  systole  (systolic  dead  point)  the 

valves  close  rapidly  and  then  reopen, 
if  systole  is  not  followed  by  diastole. 

4.  That  when  diastole  follows 
systole,  the  valves  (which  were 
already  closed  at  the  systolic  dead 
point)  extend  towards  the  conus 
arteriosus  of  the  ventricle,  forming 
with  their  surfaces  a  tetrahedron, 
with  the  point  directed  .upwards, 
and  emit  a  short  sound  which  is  of 
higher  pitch  than  the  preceding. 

From  these  results  it  is  obvious 
that  the  closing  of  the  semilunars 

Fio.  5(3. -Diagrammatic  section,  life  size,    jg      the      effect      IlOt      of     Commencing 
across    sinus    of    art.    pulmonaris    of  ,  _O 

pig:    constructed   by    Ceradini  from     diastole,    but    ol    the    close    of    Systole. 

It  is  easy  to  see   that  no  reflux   is 
possible  under  these  conditions,  since 
the  largest  ami  'the  least  equilateral   thcvalves  are  already  closed  at  the 

triangle  that  can  be  described  by  the    ...  .,        , .  •;  ,  , 

three  outlines  (oCb,  cDh,  i>A<i)  of  the   beginning    oi     diastole,    and     when 


sinuses  of  Valsalva.      The  circle  snr-  4- V, -,,,-.  ,,,„     i^f/-*  ,-vlr.ofirt    f n-nnlnn     Af\ 

rounding  the  smallest  triangle  repre-  thrOWll    intO  elastic    tension     QO     uuu 

sents  the  projection  of  the  constric-  J^ggp  Up  this  position  of  closure, 
tion    of    the    artery    which    divides  ,  .     ., 

the  sinoid  from  th«  buibar  portion.         When,    according    to    Ceradini s 
*"aghj  method,  diastole  is  imitated  by  start- 
lhe  ing  with  the   half-open   position   of 
the  valves,  their  closure  is  obtained 

by  a  reflux,  and  the  amount  of  fluid  which  under  these  condi- 
tions regurgitates  from  artery  to  ventricle  can  be  measured. 
According  to  Ceradini,  this  would  be  considerable,  amounting  to  a 
seventh  part  of  the  flow  that  leaves  the  ventricle  at  systole.  This 
proves  the  importance  of  the  pre-diastolic  closure  of  the  semilunar 
valves,  which  normally  prevents  the  loss  of  a  considerable  part  of 
the  useful  effect  of  the  cardiac  cycle. 

In  repeating  the  experiment,  with  Ceradini's  apparatus,  we 
found  several  inconveniences,  which  we  attempted  to  eliminate  by 
modifications  indispensable  to  the  demonstration  of  the  play  of  the 
valves  before  any  large  audience.  Fig.  57  shows  this  improved 
apparatus. 

The  theoretical  explanation  of  the  mechanism  of  the  valves 


VII 


MECHANICS  OF  THE  HEAET 


189 


as  elucidated  by  Csradini,  is  founded  on  simple  laws  of  hydro- 
dynamics. The  engineer  Darcy  (1857)  demonstrated  that  fluids 
passing  through  a  tube  are  not  under  the  same  pressure,  nor  do 
they  move  with  the  same  velocity,  in  the  different  lines  into  which 
the  fluid  cylinder  can  theoretically  be  analysed.  The  velocity  is 
greatest,  the  pressure  lowest,  in  the  axial  threads  ;  in  the  peripheral 
lines  the  velocity  is 
lowest  and  the  pres- 
sure greatest.  This 
law  was  confirmed  a 
year  later  by  the  re- 
searches of  Ludwig, 
who  employed  new 
and  ingenious  meth- 
ods. In  order  to  esti- 
mate the  different 
velocities  of  the  lines 
of  current,  he  em- 
ployed opaque  gran- 
ules of  lycopodium 
powder,  suspended  in 
water  running  through 
a  glass  tube.  To  esti- 
mate the  difference  in 
pressure,  he  observed 
the  direction  of  the 
current  in  a  bent  tube, 
introduced  into  the 
main  tube  in  such  a 
way  that  one  aperture 
was  just  inside  the 
wall  of  that  tube, 
whilst  the  other  pro- 
jected farther  towards 
the  axis  of  the  current. 
Ceradini  further 
showed  that  when  a 
piston  was  pushed  in- 
to a  cylindrical  glass 
tube,  held  in  the  ver- 
tical position,  and  half  filled  with  water  in  which  lycopodium 
seeds  are  suspended,  a  centripetal  eddy  may  be  observed  at  the 
base  of  the  fluid  cylinder  depressed  by  the  piston,  and  a  centri- 
fugal eddy  at  the  other  end.  When  the  movement  of  the  piston 
ceases,  the  water  cylinder  breaks  up  momentarily  into  an  inner 
cylinder,  which  continues  to  move  forward,  and  an  outer  ring, 
which  moves  backward,  united  by  a  centripetal  eddy. 


FIG.  57. — Apparatus  for  demonstrating  mechanism  of  semi- 
lunar  valves.  B,  liulb  of  art.  pulmoriaris  from  heart  of 
recently  killed  pig;  J's,  sinus  of  Valsalva  ;  S,  Riidinger's 
speculum,  closed  at  one  end  by  a  simple  glass  plate  ;  1', 
elastic  rubber  syringe,  with  which  systole  and  diastole  can 
be  imitated  by  hand  ;  fa,  valve  by  which  water  can  be 
aspirated  in  diastole  from  a  receiver,  and  then  raised, 
during  systole,  to  the  constant  level  of  an  upper  vessel  fixed 
at  a  height  which  corresponds  to  the  mean  blood  pressure 
of  the  pulmonary  artery  in  the  living  animal. 


190  PHYSIOLOGY  CHAP. 

When  water  containing  a  lycopodium  suspension  is  made  to 
circulate  through  a  glass  tube  of  small  bore,  which  after  a  short 
distance  continues  as  one  three  or  four  times  larger  in  diameter,  it 
is  easy  with  a  lens  to  see  that  there  is  a  centripetal  eddy  at  the 
point  where  the  tube  suddenly  widens,  at  which  the  lycopodium 
granules  at  the  base  of  the  dilatation  become  central  instead  of 
peripheral  in  position,  and  move  towards  the  axis  of  the  current, 
where  their  velocity  is  greatly  accelerated. 

This  experiment,  which  we  have  demonstrated  for  over  forty 
years,  is  well  adapted  to  explain  the  mechanism  of  the  semilunar 
valves.  Hesse  and  Krehl  showed  that  in  systole  the  arterial 
orifices  are  reduced  by  the  contraction  of  the  longitudinal  fibres, 
which  invest  the  inner  wall  of  the  coni  arteriosi,  to  narrow  fissures, 
above  which  is  the  marked  dilatation  formed  by  the  sinus  Valsalvae 
and  the  bulbi  arteriosi.  It  is  clear  that  the  systolic  current  that 
Hows  out  during  systole  and  passes  the  contracting  orifices  must 
make  a  centripetal  vortex  in  the  sinus  Valsalvae,  which  hinders 
the  semilunar  valves  from  opening  completely,  by  tending  to 
throw  them  into  the  closed  position.  So  long  as  the  systolic 
efflux  continues,  they  can  only  vibrate  round  the  half-opened 
position  ;  but  as  soon  as  the  efflux  ceases,  the  centripetal  vortex 
continues,  owing  to  the  force  acquired  from  the  blood,  and  imme- 
diately flings  the  valves  into  the  position  of  closure.  This 
closure,  which  would  only  be  temporary,  becomes  permanent  from 
the  fact  that  the  column  of  blood  in  the  artery  presses  hard 
against  the  valves  directly  diastole  commences. 

This  mechanism  of  the  opening  and  closing  of  the  semilunar 
valves  furnishes  the  best  and  most  rational  explanation  of  the 
many  which  have  come  under  discussion.  Tigerstedt  has  explicitly 
adopted  it  in  a  recent  synthetic  review  (1902).  But  he  errone- 
ously attributes  the  theory  to  Krehl,  forgetting  that  it  was  clearly 
formulated,  and  fully  developed  and  illustrated,  by  Ceradini,  in  a 
memoir  republished  in  the  German  language  as  early  as  1872. 

IV.  The  mechanism  of  the  auriculo- ventricular  valves  is 
essentially  similar  in  type  to  that  of  the  semilunars;  but  con- 
tains in  addition  other  secondary  features,  which  reinforce,  and 
at  the  same  time  complicate,  the  physiological  function  of  the 
valves. 

The  auriculo- ventricular  valves  (tricuspid  and  mitral)  consist 
of  tubular  membranes,  which  take  origin  in  the  fibrous  rings  at 
the  base  of  the  ventricles,  and  divide  into  three  (tricuspid)  or  two 
(bicuspid  or  mitral)  flaps  (Fig.  58). 

These  flaps  are  united  by  tendinous  cords  (chordae  tendineae) 
—which  are  attached  partially  to  the  free  border,  partially  to  the 
inferior  surface  of  the  valvular  cusps — with  the  pillars  formed  by 
the  larger  papillary  muscles,  or  the  coluinnae  as  they  emerge  from 
the  walls  of  the  ventricle.  The  mitral  valves  are  more  solidly 


VII 


MECHANICS  OF  THE  HEAET 


191 


constructed  than  the  tricuspid,  to  meet  the  greater  force  they  have 
to  encounter. 

Kiirschner  (1844)  was  the  first  to  show  that  not  a  few  of  the 
muscular  fibres  descend  from  the  auricle  to  the  superior  or  internal 
surface  of  the  valvular  fibres.  Oehl  (1861)  described  small  muscle 
bundles  which  accompany  the  larger  cords  of  the  mitral  valves. 


IJ 

Fio.  58. — A,  Mitral  valve  of  man,  seen  from  below.  The  whole  valvular  ring  has  been  spread  out 
in  one  plane,  by  a  section  through  the  median  line  of  the  great  Hap.  B,  Tricuspid  valve  of 
man,  seen  from  below.  The  valvular  ring  has  been  cut  at  the  junction  of  the  antero-exterrial 
and  the  internal  flaps.  P.u,  Anterior  papillary  muscles;  I'.p,  posterior  papillary  muscles; 
M.d,  right  flap  of  mitral  valve  ;  M.g,  left  flap  of  mitral  ;  '/.<?.«,  exterior  and  anterior  flaps  of 
tricuspid  ;  T.e.p,  exterior  and  posterior  flaps  of  tricuspid  ;  T.  i,  interior  flap  of  tricuspid  ;  L,  7., 
accessory  tongue  of  valves  ;  A,  great  arch  of  free  border  of  valves  ;  «,  a,  small  arch  of  free 
border  of  valves.  I,  Tendinous  cords  of  first  order  ;  II,  tendinous  cords  of  second  order  ;  III, 
tendinous  cords  of  third  order.  (Marc  See.) 

Paladino  (1876)  described  muscle  fibres  that  are  continued  from 
the  base  of  the  ventricle  to  the  lower  or  internal  surface  of  the 
valves. 

It  is  certain  that  without  these  valves,  with  which  the  auriculo- 
ventricular  orifices  are  provided,  not  .a  single  drop  of  blood  could 
pass  from  the  ventricles  to  the  arteries  during  systole ;  it  would 
all  be  forced  back  into  the  auricles  and  veins,  where  the  pressure  is 
very  low. 

Many  theories  are  current  about  the  function  of  these  valves, 


192  PHYSIOLOGY  CHAP. 

and  are  correct  up  to  a  certain  point,  but  are  all  more  or  less 
incomplete  and  inadequate.  A  complete  theory  can  only  be 
obtained  by  weaving  the  several  partial  hypotheses  together. 

Prior  to  Lower  (1679)  there  was  no  well-founded  theory  of  the 
mechanism  of  the  auriculo- ventricular  valves. 

He  formulated  a  theory  of  the  passive  systolic  closure  of  these 
valves  by  regurgitation  of  the  blood,  which  had  a  great  success. 
Vieussens,  Winslow,  Haller,  Senac,  Magendie  and  others  adopted 
much  the  same  opinion. 

Meckel  (1825)  and  Parchappe  (1848)  brought  forward  a  very 
different  theory,  and  admitted  an  active  systolic  closure  of  the 
auriculo-ventricular  orifice  by  approximation  of  the  folds  of  the 
valves,  which  are  kept  tense  by  the  papillary  muscles  connected 
with  them.  This  theory,  too,  found  its'  followers,  including 
Berard,  Surmay,  and  See,  the  last  of  whom  (reasoning  from  the 
position  of  the  valves  in  the  hardened  human  heart)  modified  it  in 
several  particulars,  while  retaining  the  main  idea  of  an  active 
systolic  closure.  This  theory,  like  the  preceding,  assumed  a 
certain  reflux  of  blood  from  ventricle  to  auricle.  The  difference  is, 
that  while  on  the  former  it  was  the  reflux  that  closed  the  valves, 
on  the  latter  it  is  the  movement  of  active  closure  of  the  valve  that 
drives  back  some  at  least  of  the  blood  contained  in  the  conus 
valvularis  into  the  auricles. 

Kiirschner  (1840)  was  the  first  to  ascribe  an  active  function  in 
the  expulsion  of  the  blood  to  the  cuspid  valves.  He  admitted, 
even  if  obscurely,  that  there  must  be  a  presystolic  closure  of  the 
valves,  brought  about  more  particularly  by  the  contraction  of  the 
auriculo- valvular  fibres,  which  he  described.  At  the  beginning  of 
systole  the  valves  are  tense,  and  the  chordae  tendineae  prevent 
their  reversal  into  the  auricular  cavity;  with  the  progress  of 
systole,  however,  they  are  drawn  down  by  the  contraction  of  the 
papillary  muscles,  and  thus  assist  in  emptying  the  ventricles  in 
the  direction  of  the  arteries. 

Baumgarteu  (1843)  and  Weber  (1848)  adopted  these  theories  ; 
and,  in  order  to  give  a  more  satisfactory  explanation  of  the  pre- 
systolic closure  of  the  auriculo-ventricular  orifices,  they  included 
in  their  considerations  the  low  specific  gravity  of  the  valves,  in 
consequence  of  which  they  open  with  a  light  pressure,  as  well  as 
the  elastic  tension  into  which  the  ventricles  are  thrown  as 
the  effect  of  the  presystolic  wave.  The  same  explanation  was 
adopted  by  Ludwig,  Friedreich,  Vierordt,  and  others  in  Germany. 

In  France,  Kiiss,  with  the  intention  of  further  developing  and 
completing  Kiirschner's  theory,  proposed  a  new  hypothesis.  He 
assumed  that  a  hollow  cone  was  formed  during  systole,  in  conse- 
quence of  the  contraction  of  the  papillary  muscles,  which,  as  it 
descends  into  the  ventricular  cavity,  tends  to  bring  the  segments 
of  the  valves  into  close  proximity  with  the  walls  of  the  ventricle, 


vii  MECHANICS  OF  THE  HEART  193 

which  is  simultaneously  brought  nearer  the  valves  by  the  efflux 
of  blood  from  the  arteries.  The  effect  of  this  mechanism  would  be 
a  negative  pressure  in  the  auricle  during  systole.  But  the  idea 
that  the  valves,  when  the  heart  is  functioning  normally,  can  form  a 
sort  of  hollow  cone  during  systole,  which  presses  into  the  cavity  of 
the  ventricles  like  a  stamp,  is  contradicted  by  the  observations  of 
Krehl,  as  already  cited. 

In  order  to  form  a  correct  notion  of  the  mechanism  of  the 
auriculo-ventricular  valves,  it  is  indispensable  to  determine  their 
position  during  the  entire  period  of  perisystole,  presystole,  and 
systole. 

1.  During  perisystole,  a  centrifugal  eddy  of  regurgitation  must 
be  produced  at  the  base  of  the  ventricles  by  the  kinetic  energy  of 
the   blood   which  is  rushing  from  the  auricles  to  the  ventricles. 
This  vortex,  directed  from  apex  to  base  of  the  ventricle,  is  capable 
of  maintaining  the  folds  of  the  valves  (which  are  easily  floated  in 
consequence  of  their  light  weight)  in  the  half-open  position. 

2.  During  presystole,  ventricular  pressure  is  slightly  increased, 
owing  to  the  wave  of  blood  that  is  driven  from  auricle  to  ventricle. 
The  walls  of  the  ventricle  dilate  passively,  and  are  thrown  into 
elastic  tension,  while  the  wave  of  regurgitation  from  the  centri- 
fugal vortex  increases,  and  the  borders  of  the  valvular  folds  tend 
to  approach,  and  take  up  a  position  approximating  to  closure. 
The  auriculo-valvular  fibres  of  Kiirschner  contract  simultaneously, 
which   tends  to  shorten   the  valves    and  maintain  them  in  the 
upright  position. 

3.  At  the  presystolic  dead  point  there   is  a  cessation  of  the 
flow  from  auricle  to  ventricle,  while  the  centrifugal  vortex  persists, 
in  consequence  of  the  dynamic  force  acquired  by  the  blood ;  this 
causes  the  valves  to  close  with  perfect  apposition,  not  merely  of 
their  borders,  but  also  of  a  considerable  portion  of  their  internal  or 
superior  surfaces. 

4.  At  the  commencement   of  systole    the   valves   which   are 
already  closed  expand  and  vibrate,  in  consequence  of  the  sudden 
rise  of  ventricular  pressure,  and  form  an  irregularly  curved  arch  at 
the  level  of  the  auriculo-ventricular  orifice.    This  can  be  detected  in 
larger  animals  by  passing  the  finger  through  an  opening  made  in 
the  auricular  appendix,  as  far  as  the  auriculo-ventricular  orifice 
(Chauveau),  and  results  from  the  varying  lengths  of  the  chordae 
tendineae  affixed  to  the   inferior  surface   of   the  valvular  folds 
(Krehl,  Fig.  59). 

5.  During  the  systolic  evacuation  of  the  ventricle,  the  auriculo- 
ventricular  orifice  becomes  more  and  more  restricted  until  it  almost 
entirely  closes.     At  the  same  time  the  valvular  folds  are  drawn 
forcibly  onwards  by  the  contraction  of  the  papillary  muscles,  so 
that  increasingly  larger  portions  of  their  inner  or  upper  surface  are 
brought  fully  into  contact,  and  deflected  so  as  to  become  vertical. 

VOL.  i  o 


194  PHYSIOLOGY  CHAP. 

The  synchronous  contraction  of  the  ventriculo- valvular  fibres 
augments  their  expulsive  efficiency. 

In  this  complex  theory  of  the  mechanism  of  the  auriculo- 
ventricular  valves  (which  we  have  insisted  on  for  thirty  years), 
the  fact  which  is  usually  less  generally  accepted  is  that  of 
the  presystolic  closure  of  the  venous  orifices,  which  we  hold  to 
be  an  indispensable  condition  of  the  normal  exclusion  from  the 
systole  of  all  trace  of  reflux  from  ventricles  to  auricles.  Chauveau, 
while  maintaining  the  theory  of  Klirschner,  says  expressly  that 
"  les  valvules  auriculo-ventriculaires  sont  pendantes  a  la  fin  de  la 
systole  auriculaire  "  (1876) ;  without  considering  that  if  this  pheno- 
menon (which  in  his  experiments  is  obviously  the  result  of 
weakened  functions  in  the  exposed  heart  of  the  horse,  injured, 

moreover,  by  the  introduction  of  the 
finger  into  the  auricle)  were  normal, 
there  would,  under  physiological 
conditions,  be  a  pronounced  reflux 
of  blood  into  the  auricle  at  the  be- 
ginning of  systole,  synchronously 
with  the  sharp  rise  of  the  valves. 
For  it  is  clear  that  at  systole  the 
pressure  increases  not  only  in  the 
blood  that  is  beneath  the  valves,  but 
also  in  that  which  lies  along  the  axis 
of  the  ostiuin,  and  which  can  flow 
back  freely  so  long  as  the  valves  are 
not  closed. 

The      mechanism     of     valvular 

no.  sp.-DiaKr.mi  showing  position  of  closure   at   the  systolic   dead   point 
auricuio-ventricuiar  flaps  of  valves  at  is    demonstrated    by   the    following 

commencement  of  systole,   owing  to  .  ^  ,    , 

puii  of  chordae  tendinae.  (Krehi.)       experiment  upon  the  excised  heart 

of  man,  pig,  or  other  large  mammal. 

The  cardiac  cavity  must  be  washed  free  of  clot,  and  corks 
fixed  in  the  aorta  and  pulmonary  artery,  which  are  cut  off  short ; 
the  two  auricular  cavities  are  then  opened  freely  from  above, 
and  the  margins  of  the  openings  attached  to  an  iron  ring  upon 
a  support  (Fig.  60)  without  tearing  or  deforming  the  base  of 
the  ventricles.  When  the  valves  are  normal,  and  rigor  mortis 
has  passed  off,  it  is  only  necessary  to  fill  the  two  ventricles  and 
the  funnel-shaped  cavity  formed  by  the  walls  of  the  auricles 
with  water,  in  order  to  see  how  the  valves  float  up  and  assume 
the  half-open  position.  If  presystole  be  now  imitated,  by 
injecting  a  few  c.c.  of  water  with  a  powerful  syringe,  the  nozzle 
of  which  is  directed  towards  the  centre  of  the  (right  or  left) 
auricuio-ventricuiar  ostium,  a  marked  rise  of  the  valvular  flaps 
will  be  seen,  with  such  approximation  of  the  borders  that  the 
orifice  is  converted  into  a  narrow  slit,  in  consequence  of  the 


VII 


MECHANICS  OF  THE  HEAET 


195 


centrifugal  vortex  and  subsequent  wave  of  regurgitation,  which 
drives  the  valves  upward,  and  tends  to  close  them.     So  soon  as  the 


FIG.  60.— Apparatus  to  demonstrate  presystolic  closure  of  auriculo-ventricular  valves.  The  two 
figures  represent  the  same  normal  heart  of  a  young  subject.  The  two  arteries,  aorta  and 
pulmonary,  are  divided  near  the  orifices,  and  ligatured  to  corks.  The  walls  of  the  auricle  are 
opened  above  and  stitched  to  an  iron  ring  clamped1  to  a  support.  On  tilling  the  cavity  of  the 
heart  with  water,  the  auriculo-ventricular  valves  are  seen  to  float  into  the  semi-open  position 
(upper  figure).  After  injection  of  a  few  c.c.  of  water  in  the  direction  of  the  axes  of  both 
orifices,  the  valves  temporarily  assume  the  position  of  perfect  closure  (lower  figure). 

injection  ceases,  the  flaps  of  the  valves  suddenly  come  together, 
closing  the  ostium  completely  for  the  space  of  a  few  seconds. 


196  PHYSIOLOGY  CHAP. 

This  shows  that  the  persistence  of  the  centrifugal  vortex  produced 
by  the  kinetic  energy  of  the  injected  fluid,  is  of  itself  an  adequate 
mechanical  condition  to  secure  the  perfect  function  of  the  valvular 
apparatus,  without  the  slightest  regurgitation  from  ventricle  to 
auricle — even  if  we  admitted  that  presystole  is  not  immediately 
succeeded  by  systole,  biit  that  a  period  of  intersystole  constantly 
intervenes,  as  has  been  proposed  by  Chauveau  (infra,  p.  201). 

V.  The  acoustic  phenomena  which  accompany  the  cycle  or 
cardiac  revolution  are  intimately  connected  with  the  valvular 
mechanism. 

When  the  heart  of  a  healthy  person  is  auscultated  directly 
with  the  ear  or  with  the  stethoscope,  two  distinct  murmurs  are 
heard,  known  to  physicians  as  the  cardiac  sounds. 

No  one  prior  to  Laennec  (1819)  had  grasped  the  diagnostic 
importance  of  these  sounds.  Harvey,  whose  panegyrists  claim 
that  he  was  the  first  to  describe  them,  confines  himself  to  stating 
that  at  the  moment  when  the  pulse  is  perceptible,  a  murmur  can 
simultaneously  be  heard  in  the  chest.  That  is,  he  merely  detected 
the  systolic  sound,  and  rightly  named  it  a  murmur,  since  it  has  all 
the  properties  of  the  latter,  and  can  with  difficulty  be  determined 
as  a  musical  tone. 

Nothing  is  easier  under  physiological  conditions  than  to  dis- 
tinguish the  first  from  the  second  sound :  the  first  is  longer, 
deeper,  duller ;  the  second  is  shorter,  sharper,  clearer.  The  second 
sound  is  followed  by  a  long  pause,  while  between  the  first  and 
second  there  is  a  lesser  pause. 

Since  the  first  sound  is  systolic,  i.e.  it  persists  throughout 
almost  the  entire  systole,  Laennec  assumed  that  the  first  was 
the  effect  of  the  systolic  efflux  from  ventricles  to  arteries,  the 
second,  of  the  diastolic  afflux  from  auricles  to  ventricles,  due  to  the 
auricular  systole  or  presystole. 

It  was  easy  for  Turner  (1829)  to  refute  the  second  part  of  this 
theory,  by  showing  that  the  second  or  short  sound,  since  it  succeeds 
immediately  to  the  first  or  long  sound,  coincides  with  the  commence- 
ment only  of  ventricular  diastole  (or  perisystole),  and  cannot  there- 
fore be  the  result  of  the  auricular  systole  (or  presystole). 

Still  more  erroneous  is  Magendie's  theory  (1835),  which 
assumed  that  the  first  sound  was  the  effect  of  the  impact  of  the 
apex  of  the  heart  against  the  thoracic  wall  in  systole,  and  the 
second  of  the  impact  of  the  base  during  presystole.  The  sounds 
persist  even  after  the  thoracic  cavity  has  been  opened,  and  the 
heart  exposed. 

The  so-called  valvular  theory  of  cardiac  sounds  was  first 
formulated  by  Carswell  and  Kouanet  (1832).  Starting  from -the 
correct  observation  that  the  first  sound  is  more  acute  in  the  region 
of  the  ventricles,  and  the  second  in  that  of  the  arterial  orifices; 
they  admitted  that  the  first  depended  on  the  vibrations  of  the 


vii  MECHANICS  OF  THE  HEAET  197 

venous  auriculo- ventricular  valves,  the  second  on  the  vibration  of 
the  arterial  or  semilunar.  They  also  succeeded  in  producing  an 
artificial  sound  in  an  excised  aorta,  by  throwing  the  valves  into 
sudden  tension. 

Williams  and  the  Dublin  Committee  of  the  British  Association 
(1835)  undertook  to  test  this  theory,  and  confirmed  by  ingenious 
experiments  the  part  which  referred  to  the  second  sound.  They 
noted  that  the  second  sound  was  abolished  when  the  play  of  the 
semilunar  valves  was  impeded,  as  when  the  apex  was  cut,  and  the 
blood  prevented  from  issuing  by  the  arteries.  They,  however, 
found  the  valvular  theory  to  be  incorrect  as  regards  the  first 
sound,  observing  that  it  persisted  even  when  the  heart  was  void  of 
blood  and  excised  from  the  animal.  Accordingly  they  postulated 
a  purely  muscular  origin  for  the  first  sound — a  theory  that  was 
taken  up  later  on  by  Ludwig  and  Dogiel  (1868),  and  confirmed  by 
numerous  experiments. 

Wollaston  had  already  shown  in  1810  that  the  contraction  of 
a  muscle  can  produce  a  bruit.  Ludwig  further  showed  that 
the  muscles  of  the  ventricle,  which  are  interwoven  in  various 
intricate  ways,  and  form  two  cavities  with  trabeculated  inner 
surface,  must  be  better  able  than  skeletal  muscles  to  generate  a 
bruit  when  suddenly  thrown  into  tension. 

The  demonstration  of  the  muscular  theory  does  not,  however, 
exclude  there  being  some  truth  in  the  valvular  theory  of  the  first 
sound.  Wintrich  (1875),  by  means  of  Helmholtz'  resonators, 
succeeded  in  analysing  the  first  sound,  and  recognised  it  to  be  the 
result  of  two  components :  a  deep  sound  (or  rumble)  of  a  muscular 
character,  and  one  or  more  sharp  tones,  depending  not  merely 
upon  the  vibrations  of  the  auriculo -ventricular,  but  also  upon 
those  of  the  semilunar  valves,  demonstrated,  as  above,  by 
Ceradini. 

Even  with  these  additions,  however,  the  theory  of  the  sounds 
of  the  heart  was  incomplete.  Talma  (1880)  examined  the  valvular 
theory  from  the  standpoint  of  the  laws  of  acoustic  vibrations,  and 
objected  that  since  the  valves  are  immersed  in  a  fiuid  of  lower 
specific  gravity  than  themselves,  the  sounds  that  are  generated  when 
they  are  thrown  into  sudden  tension  must  essentially  depend  upon 
the  vibrations  of  the  blood,  rather  than  on  those  of  the  valves. 

Webster  (1882),  however,  showed  that  Talma  had  overlooked 
one  fact,  namely,  that  both  the  first  and  second  sounds  can  be 
resolved  into  several  components,  by  the  help  of  a  resonator.  He 
attempted  to  prove  that  the  effects  of  the  vibrations  of  the  semi- 
lunars  and  also  of  the  walls  of  the  bulbi  arteriosi,  can  be  dis- 
tinguished from  the  effects  of  the  vibrations  of  the  blood  in  the 
second  sound.  To  this  we  would  add  that  the  valvular  vibrations 
that  contribute  to  the  formation  of  the  second  sound,  coincide,  not 
with  the  dosing  of  the  valves,  as  is  stated  in  every  text-book,  but 


198  PHYSIOLOGY  CHAP. 

with  the  tension  into  which  they  are  thrown  after  closure,  when 
the  ventricular  diastole  commences. 

In  conclusion,  we  may  admit  the  following  points  as 
established  :— 

1.  The  systolic  sound  is  essentially  a   muscular   bruit,  with 
which  higher  tones  are  associated  that  depend  on  the  vibrations  of 
the  auric ulo- ventricular  valves,  the  semilunars,  and  the  mass  of 
the  blood. 

2.  The  post-systolic  sound  is  the  result  of  higher  tones  depending 
on  the  vibration  either  of  the  semilunars  and  the  bulbi  arteriosi 
when  thrown  into  tension,  or  of  the  mass  of  the  blood. 

The  importance  of  the  heart-sounds,  from  a  physiological  stand- 
point, consists  in  recognising  them  as  the  external  signs  of  the 
duration  of  the  phases  of  the  cardiac  cycle,  since  there  is  good 
reason  for  assuming  that  the  commencement  of  the  first  sound 
coincides  with  the  commencement  of  systole,  the  commencement 
of  the  second  sound  with  the  commencement  of  diastole ;  and  that 
the  interval  between  the  first  and  second  sounds  represents  the 
duration  of  systole,  the  interval  between  the  second  and  first,  the 
duration  of  perisystole  plus  presystole.  We  shall  see  how  Edgren 
has  applied  these  criteria. 

It  is  not  the  physiologist's  task  to  make  any  profound  examina- 
tion of  the  pathological  changes  in  the  heart's  sounds,  or  to  go  into 
their  great  significance  from  the  diagnostic  and  clinical  standpoint. 
But  in  so  far  as  these  changes  are  a  proof,  and  a  further  illustration, 
of  physiological  theory,  the  most  general  aspects  of  them  may  be 
summed  up  in  a  few  words. 

Cardiac  sounds  under  pathological  conditions  may  be  reinforced 
or  weakened,  according  as  the  heart's  action  is  stronger  or  weaker 
than  in  the  normal  state.  The  first  may  be  a  sign  of  hypertrophy, 
the_second  of  degeneration,  of  the"" myocardium. 

In  auricular  hypertrophy  there  may  be  a  presystolic  murmur, 
immediately  preceding  the  systolic,  giving  the  effect  of  a  duplica- 
tion or  abnormal  lengthening  of  the  first  sound.  On  the  other 
hand  there  may  be  a  real  doubling  of  the  second  sound,  when  the 
tension  of  the  aortic  seinilunar  valves  (which  normally  have  to 
bear  a  greater  pressure)  precedes  that  of  the  semilunars  of  the 
pulmonary  (which  normally  sustain  less  pressure)  in  marked 
degree. 

In  stenosis  of  the  orifices  and  in  valvular  insufficiency  the 
sounds  are  replaced  by  "  blowing  "  murmurs,  which  are  produced 
by  the  vibrations  of  the  blood  as  it  passes  through  the  narrowed 
orifices  or  imperfectly  closed  valves. 

In  these  can  be  distinguished  : — 

(a)  Post-systolic  murmurs,  the  diagnostic  sign  of  insufficiency 
of  aortic  or  pulmonary  semilunars,  according  as  they  are  more 
audible  in  the  region  of  the  origin  of  the  aorta  (right  sternal 


VII 


MECHANICS  OF  THE  HEART 


199 


border  between  the  first  costal  and  second  intercostal  space)  or  in 
that  of  the  pulmonary  artery  (left  sternal  border,  at  the  level  of 
the  second  intercostal  space).  (Fig.  61,  Ad  and  As.) 

(b)  Presystolic  murmurs,  the  diagnostic  sign  of  stenosis  of  the 
right  or  left  auriculo-ventricular  orifice,  according  as  it  is  more  or 
less  audible  in  the  region  of  the  right  ventricle  (external  border 
of  sternum  at  the  level  of  the  fourth  intercostal  space),  or  in  the 


FIG.  61.— Semi-diagrammatic  figure  of  topography  of  the  heart  and  its  .relations  with  the  lungs 
and  thorax.  Vd,  Auscultation  point  of  right  ventricle ;  Vs,  auscultation  point  of  left 
ventricle ;  AJ,  auscultation  point  of  aorta  ;  Ax,  auscultation  point  of  pulmonary  ;  A,  aorta ; 
P,  pulmonary  artery  ;  cs,  vena  cava  superior  ;  i,  •/,  innominate  artery  and  vein  ;  .<?,  *,  subclavian 
artery  and  vein ;  c,  c,  carotid  arteries ;  g,  g,  jugular  veins  ;  pe,  dotted  line  to  show  limit  of 
lungs  in  inspiration ;  pi,  continuous  line  showing  limit  of  lungs  in  expiration  ;  1-10,  1st  to 
10th  ribs. 

region  of  the  left  ventricle  (left  mamillary  line  in  the  fourth  or 
fifth  intercostal  space).     (Fig.  61,  Vd  and  Vs.) 

(c)  Systolic  murmurs,  the  diagnostic  sign  either  of  insufficiency 
of  the  venous  valves  (bicuspid  or  tricuspid),  or  of  stenosis  of 
the  arterial  orifices  (aortic  or  pulmonary),  according  as  it  is 
more  conspicuous  at  one  or  other  of  these  four  points.  Systolic 
murmurs  are  distinguished  from  the  preceding  by  their  greater 
accentuation,  since  they  are  produced  by  stronger  vibrations,  and 
by  the  fact  that  the  thoracic  walls  vibrate  along  with  them 


200 


PHYSIOLOGY 


CHAP. 


(fremitus),   as   can   be  perceived  on  laying  the   hand  upon  the 
precordial  region. 

The  mechanical  deficiencies  of  the  heart  can  be  compensated 


rt  ,C  ^3  O  ,C  .U 

ill  ill 

^  -c  "3  H  -S  5 


Pi 


l 

^ 


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-o  b  u  £  is'"' 


I    all 


O 


so  that  patients  may  live  for  many  years.  This  compensation 
depends  essentially  upon  hypertrophy  of  the  myocardium;  more 
particularly  upon  hypertrophy  of  the  ventricles,  in  cases  of 
valvular  insufficiency — upon  hypertrophy  of  the  auricles  in  arterial 
stenosis. 


vii  MECHANICS  OF  THE  HEART  201 

VI.  In  order  to  comprehend  the  nature  of  the  evacuation  and 
refilling  of  the  heart,  it  is  important  to  make  an  experimental 
study  of  the  oscillations  of  pressure  within  the  auricles  and  the 
ventricles,  in  presy stole,  systole,  and  perisy stole. 

These  observations  were  first  made  by  Chauveau  and  Marey 
(1861)  on  the  horse,  by  means  of  the  so-called  cardiographic 
sound,  in  conjunction  with  a  tambour  and,  lever  writing  upon 
a  rotating  cylinder  (Figs.  62  and  63).  The  modifications  in 
instrument  and  method  made  by  Fick,  von  Frey,  Hiirthle,  Roy, 
Fredericq,  Bayliss  and  Starling,  and  Porter,  have  led  to  results 
which  differ  in  certain  important  points  from  those  of  the  two 
French  investigators. 

In  the  original  researches  of  Chauveau  and  Marey,  the  tracings 
of  the    oscillations   of  pressure   in  the  right  auricle  were  very 
imperfect,  owing  possibly  to  insufficient  sensibility  of  the  elastic 
ampulla  introduced  into 
the  said  cavity.     At  the 
Rome   Congress  (1894), 
Chauveau  corrected  cer- 
tain errors  of  Marey,  on 
the    strength     of    new 
cardiographic        curves, 
obtained  from  the  horse 

by    means    Of    more    per-  FIG.    OS.  —  Marey's   tambour   with    writing   lever  (Verdin's 

fppf   PYnlnrat-nrv  csnnnrk  perfected   type).      «,    Metal  capsule  closed    by  rubber 

[eCD   eXplOiatOry  SOUnCtS.  membrane,  attached  without  tension  to  metal  ring   B. 

Thptsp        nVmprvuHnnej  The  aluminium  disc  fixed  to  the  centre  of  the  membrane 

se     oDSijrvauc  (>arries  a  writing  lever>   Special  contrivances  make  the 

Were       published       in       a          instrument  more  or  less  sensitive  by  adjusting  the  initial 
~r>  .       /_,  orkr>  position  of  the  lever,  and  bringing  the  writing  point  nearer 

Series  Of  memoirs  (1899-          to  or  farther  from  tiie  surface  of  the  moving  drum. 

1900),  which  seem  to  us 

rather  to  indicate  the  unreliability  of  results  obtained  with  the 

cardiac  sound,  than  to  add  to  the  known  data  of  cardiac  mechanism. 

Let  us  examine  the  most  important  of  these  memoirs,  that 
entitled  L' Inter  systole  du  cceur  (1900).  This  Chauveau  calls  a 
phase  of  his  cardiographic  tracings,  interpolated  between  presystole 
and  systole. 

If  the  interpretation  which  he  gives  of  this  period,  interposed 
between  the  systole  of  the  auricles  and  that  of  the  ventricles,  were 
correct,  it  would  involve  a  complete  revolution  in  the  fundamental 
concepts  of  cardiac  mechanism.  To  prove  this,  it  is  only  necessary 
to  bear  in  mind  the  conclusions  above  stated  in  regard  to  the 
function  of  the  auriculo- ventricular  valves. 

These  close  at  the  end  of  presystole,  so  that  they  are 
already  shut  at  the  beginning  of  systole.  If,  however,  we  admit 
an  intersystolic  phase,  then  the  said  valves,  not  being  kept 
in  the  position  of  closure  by  rise  of  ventricular  pressure,  would 
reopen,  and  thus  render  useless  the  entire  apparatus  described 
above  for  closing  them. 


202  PHYSIOLOGY  CHAP. 

Chauveau,  disregarding  the  conclusions  of  Ceradioi  (whom  he 
does  not  mention),  maintains  on  the  ground  of  obscure  experiments 
and  complicated  arguments,  that  the  contraction  of  the  papillary 
muscles  of  the  ventricles  occurs  during  his  "  intersystole,"  with  the 
object  of  disposing  the  flaps  of  the  auriculo- ventricular  valves  in 
such  a  manner  that  the  systolic  rise  in  ventricular  pressure  (which, 
according  to  him,  brings  about  the  valvular  closure)  may  impinge 
principally  not  upon  the  axial  but  upon  the  parietal  face  of  the 
valves. 

No  long  argument  is  required  to  demonstrate  the  impossi- 
bility of  this  hypothetical  doctrine.  We  know  that  the  auriculo- 
ventricular  valves  close  at  the  termination  of  presystole.  The 


FIG.  64. — Tracings  obtained  by  Chauveau  from  the  horse,  by  his  perfected  cardiographic  sound. 
I,  Oscillations  of  pressure  in  right  auricle;  II,  oscillations  of  pressure  in  right  ventricle; 
r,  return  to  abscissa;  1,  period  of  auricular  beat  (contraction  and  relaxation);  L>,  period  of 
intersystole  ;  3,  period  of  ventricular  beat  (contraction  only).  This  is  succeeded  by  the  period 
of  ventricular  diastole,  which  Chauveau  does  not  indicate. 

supposed  intersystolic  contraction  of  the  papillary  muscles, 
causing  them  to  reopen,  could  not,  even  if  it  placed  them  in  a 
position  unfavourable  to  the  systolic  reflux,  entirely  prevent  it. 
On  the  other  hand,  the  researches  of  Eoy  (1890)  show  that  the 
papillary  muscles  do  not  contract  before  the  muscular  walls  of  the 
heart,  but  enter  into  tardy  contraction,  thus  facilitating  the  almost 
complete  evacuation  of  the  ventricles  in  systole. 

Tigerstedt's  interpretation  of  Chauveau's  intersystole,  in  the 
fourth  edition  of  his  Physiologic  des  Menschen,  seems  no  less 
impossible.  He  thinks  it  depends  on  the  elastic  reaction  of  the 
walls  of  the  ventricles,  which  are  passively  distended  in  auricular 
systole,  and  which  occurs  only  in  cases  in  which  the  termination 
of  the  latter  and  the  commencement  of  the  ventricular  systole  are 
separated  by  a  considerable  time  interval.  It  is,  in  fact,  sufficient 
to  look  at  one  of  Chauveau's  curves,  especially  that  of  the  internal 


viz  MECHANICS  OF  THE  HEART  203 

pressure  of  the  auricle  and  right  ventricle,  which  he  gives  as 
typical  (Fig.  64),  to  see  that  the  intersystole  does  not  follow 
immediately  upon  simple  systole,  but  on  the  complete  pulsation  of 
the  auricle  (auricular  systole  and  diastole). 

Since,  however,  the  intersystole  coincides  with  a  sharp  rise  of 
pressure  in  the  auricle,  and  since  the  presence  of  a  sound  intro- 
duced between  the  flaps  of  the  valves  may  give  rise  to  a  slight 
reflux  of  blood  from  ventricle  to  auricle,  it  seems  probable  that 
the  intersystole  depends  precisely  upon  this  slight  reflux,  coincident 
with  the  initiation  of  ventricular  systole. 

It  is  evident  from  these  data  that  the  "  intersystolic  phase  "  of 
Chauveau's  tracings  represents  no  real  fact,  occurring  during  the 
normal  cycle  of  cardiac  movement,  but  is  in  all  probability  an 
artefact,  coincident  with  the  period  of  latent  systole,  artificially 
prolonged  by  the  presence  of  the  exploring  sound  in  the  atiriculo- 
ventricular  orifice. 

But  if  this  point  in  Chauveau's  tracings  is  difficult  to  interpret, 
another  feature  offers  far  more  insuperable  obstacles,  i.e.  that  part 
of  the  pressure  curve  in  the  auricle  which  corresponds  to  the 
ventricular  diastole,  which  Chauveau  passes  over,  keeping  silence 
on  the  subject. 

At  that  period  there  is  in  Chauveau's  curves  an  incomprehensible 
rise  of  auricular  pressure.  Now  the  observations  of  all  other 
experimenters,  carried  out  by  different  methods,  more  reliable  than 
the  sound,  have,  without  exception,  resulted  in  showing  a  negative 
pressure  in  the  ventricle  during  the  primary  phase  of  diastole. 
Since  in  diastole,  when  the  cuspid  valves  are  open,  the  auricle  and 
ventricle  form  a  single  cavity,  it  is  evident  that  the  negative 
pressure  existing  in  the  ventricle  must  be  propagated  to  the 
auricle  also. 

More  interesting  and  more  probable,  on  account  of  their 
simplicity,  are  the  researches  carried  out  by  numerous  experi- 
menters on  the  venous  pulse  of  the  cava  and  jugular  veins,  either 
in  man  or  in  animals,  which  throw  light  on  the  mode  in  which  the 
right  heart  is  filled  and  emptied. 

Among  the  authors  who  have  more  recently  been  engaged  on 
this  subject  are  Mackenzie  (1902),  Beccari  (1903),  Wenckebach 
(1906),  Fredericq  (1907).  They  have  recorded  tracings  of  the 
venous  pulse  (phlebogram)  with  a  simultaneous  record  of  the 
cardiac  pulse  (cardiogram),  or  of  the  radial  artery  (radiogram). 

In  nearly  all  healthy  people,  in  the  horizontal  supine  position, 
with  head  and  neck  a  little  lower  than  the  body,  it  is  possible  to 
detect  with  the  eye  the  pulsation  at  the  base  of  the  neck,  and  to 
take  a  tracing  of  it,  by  means  of  a  sufficiently  sensitive  exploring 
tympanum.  In  the  stage  of  convalescence  from  diseases,  accom- 
panied, as  in  jaundice,  by  weakening  of  the  heart-beat,  it  is  easy 
to  obtain  fairly  clear  phlebograms,  which  in  their  elevations  and 


204  PHYSIOLOGY  CHAP. 

depressions  faithfully  reflect  the  phases  of  activity  of  the  right 
heart. 

The  phlebograms  made  by  Wenckebach  present  three  elevations 
and  three  depressions  as  shown  in  Fig.  65. 

Elevation  (a)  coincides  with  presystole,  and  expresses  the 
temporary  arrest  of  the  venous  current  (perhaps  its  partial  reflux 
also)  during  the  contraction  of  the  right  auricle.  The  second  rise 
(0)  corresponds  with  systole  and  depends,  according  to  Mackenzie 
and  Wenckebach,  on  the  mechanical  transmission  of  the  carotid 
pulse  beneath  the  vein  that  is  being  explored.  This  is  rightly 


FKJ.  0.0. — Tracings  of  oscillations  of  pressure  in  jugular  vein  (phlebograms)  recorded  with  a  fairly 
sensitive  exploring  tambour,  applied  to  the  base  of  the  neck  in  a  youth  of  23,  recovering 
from  catarrhal  jaundice  (Wenckebach).  Sphygmograms  from  radial  artery  simultaneously 
recorded  with  the  phlebograms.  Time  marked  in  .,'n".  The  points  of  return  marked  on  the 
tracings  divide  the  period  of  pulsation  into  the  five  intervals  described  in  the  text. 

contested  by  Fredericq,  on  the  strength  of  his  researches  on  dogs, 
from  which  he  proved  that  the  rise  (c)  which  accompanies  the 
beginning  of  systole  is  due  to  the  closure  movement  of  the 
tricuspid  valve.  (Better  expressed  as,  due  to  the  projection 
towards  the  auricle  of  the  said  valve,  already  closed  at  the 
termination  of  presystole.)  The  third  rise  (v)  coincides  with  the 
tension  of  the  semilunar  valves  already  closed  at  the  termination 
of  systole,  and  probably  depends  upon  the  impulse  received  by  the 
right  auricle  in  the  dilatation  of  the  ostiuin  and  arterial  bulb  in 
consequence  of  the  wave  of  rebound  which  occurs  at  the  com- 
mencement of  diastole. 

The  depressions  of  the  phlebograms  are  more  interesting  to 
consider,  i.e.  the  two  negative  phases  of  the  venous  pressure.  The 
first  (x),  from  the  apex  of  (c)  to  the  base  of  (v),  coincides  with 
the  phaqfl  nf  ayatolic  emptying  of  the  ventricles,  and  is  due  to 
the  sinking  of  the  base  of  the  ventricle  by  which  the  a-nrimiiar 

cavity  hftftomflfl  fi^ftrt,  and  flTflrp.isfts  a.  marifftirl  fl.spirfl.t,irm  upon  the 
veins.  The  second  negative  phase  (y}  coincides  with  diastole,  and 
depends,  according  to  Wenckebach,  on  the  fact  that  during 


VII 


MECHANICS  OF  THE  HEART 


205 


ventricular  relaxation  the  blood  can  flow  freely  from  the  vein  to 
the  auricle,  from  the  auricle  to  the  ventricle,  by  the  negative 
pressure  or  aspiration  which  this  exerts  during  the  said  phase. 

L.  Fredericq,  in  his  studies  on 
dogs  (in  relation  to  cardiography 
of  the  heart  and  the  venous 
pulse,  1890-1907),  insisted  on  the 
virtual  identity  of  the  phlebo- 
grams  with  the  tracings  of  the 
variations  of  blood  pressure  with- 
in the  right  auricle,  which  he 
obtained  with  open  thorax,  on 
putting  this  cavity  into  direct 
communication  with  a  sensitive 
sphygmoscope  (Fig.  66). 

To  obtain  an  idea  of  the  in- 
dividual phases  of  the  cardiac  cycle  and  the  oscillations  of  pressure 
within  the  auricles,  ventricles,  and  large  arteries,  we  may  avail 


FIG.  i)0.  — Marey's  sphygmoscope,  which  acts  as 
an  elastic  manometer  in  connection  with 
a  tambour.  It  consists  of  a  cylindrical 
glass  tube,  closed  at  both  ends  by  rubber 
stoppers  with  a  hole  through  the  centre 
of  which  come  two  glass  tubes.  An  elastic- 
cap  is  slipped  over  the  right-hand  stopper, 
filled  with  an  anticoagulant  solution,  and 
connected  with  a  blood-vessel.  The  cap 
reacts  to  each  rise  and  fall  of  pressure,  by 
expanding  or  contracting.  The  tube  on  the 
left-hand  side  conveys  these  movements  to 
the  tambour. 


FIG.  67. — Diagram  of  cardiac  cycle  or  revolution.  The  three  curves  reproduce  the  tracings  of 
oscillations  of  pressure  obtained  simultaneously  from  the  left  auricle,  left  ventricle,  and 
aorta  of  the  dog,  by  Fredericq's  method.  The  duration  of  the  different  phases  of  the  cycle, 
and  the  time  at  which  the  heart-sounds  are  perceptible,  are  marked  on  the  abscissae ;  the 
intracardiac  and  aortic  pressures  in  mrn.  Hg,  upon,  the  ordinates. 

ourselves  of  a  diagram  constructed  from  the  data  provided  by  the 
work  of  Fredericq,  which  agree  fundamentally  with  those  admitted 
by  all  competent  physiologists  who  have  occupied  themselves  with 
the  mechanics  of  the  heart  (Fig.  67). 


206  PHYSIOLOGY  CHAP. 

The  diagram  is  so  clear  that  a  detailed  description  is  super- 
fluous. As  appears  in  the  figure,  during  presystole  (which  lasts 
for  about  the  sixth  part  of  the  time  of  the  internal  revolution) 
there  is  a  slight  rise  in  auricular  pressure  which  is  transmitted  to 
the  ventricle  also,  and  which,  as  we  shall  see,  effects  the  perfect 
closure  of  the  venous  valve  at  the  presystolic  dead  point. 

In  systole  (which  lasts  two  and  a  half  times  longer  than  pre- 
systole) two  periods  must  be  distinguished ;  the  first,  which  is 
short,  termed  the  period  of  tension  or  latent  systole ;  the  second, 
somewhat  longer,  that  of  efflux,  or  systolic  evacuation. 

The  first  corresponds  to  the  time  necessary  for  the  ventricular 
pressure  to  reach  and  exceed  the  level  of  aortic  pressure,  in  order 
to  determine  the  opening  of  the  seniilunars. 

With  the  sharp  rise  of  ventricular  pressure,  there  is  a  simul- 
taneous rise  of  auricular  pressure,  determined  by  the  tension  and 
upward  propulsion  of  the  cuspid  valves. 

The  duration  of  this  period  in  the  horse  is,  according  to  Marey,  Ol " ; 
Hiirthle,  on  the  contrary,  finds  it  to  be  for  dog  O02-O04  ",  and  Fredericq  con- 
firms this  last  figure.  For  man  the  data  vary  considerably.  Marey,  Rive, 
Landois,  Edgren  give  figures  oscillating  between  O'l "  and  O073",  'Grunmach 
indicates  a  value  of  OO7",  Keyti  0'054".  Hiirthle,  on  the  ground  of  his 
researches  on  the  dog,  calculates  the  period  of  tension  as  equal  to  0*03  "  for 
man,  a  figure  which  is  certainly  too  high. 

The  second  systolic  period  coincides  with  the  rise  of  aortic 
pressure  (arterial  pulse),  the  final  elevation  of  ventricular  pressure 
which  is  then  arrested  in  a  kind  of  plateau,  and  a  sudden  drop  of 
auricular  pressure,  until  it  falls  below  zero,  after  which  there  is 
again  a  slow  but  progressive  rise. 

Physiologists  have  long  disputed  over  that  portion  of  the  curve  of  intra- 
ventricular  pressure  which  is  known  as  the  systolic  plateau,  and  corresponds 
to  the  ventricular  efflux.  While  the  tracings  obtained  by  Cliauveau  and 
Marey  in  1863  on  the  horse,  and  all  the  subsequent  publications  of  Chanveau, 
show  an  almost  horizontal  tract  between  the  rapidly  ascending  (systolic),  and 
the  corresponding  and  rapidly  descending  (diastolic),  portions,  many  authors 
maintain  that  the  curve  which  represents  the  internal  pressure  of  the 
ventricle  is  composed  solely  of  a  rapidly  rising,  followed  by  a  correspondingly 
'rapidly  falling  portion  ;  they  deny  the  existence  of  the  systolic  plateau.  This 
point  has  recently  been 'taken  up  again  by  various  authors,  both  English  and 
American,  among  whom  are  Bayliss,  Starling,  and  Porter.  They  have  intro- 
duced important  technical  alterations  in  the  method,  which  tend  to  exclude 
instrumental  inertia. 

Bayliss  and  Starling  employed  a  manometer  containing  a  solution  of 
magnesium  sulphate,  one  arm  of  which  is  open,  and  connected  with  the 
cavity  of  the  ventricle  by  means  of  an  open  sound,  while  the  other  arm 
consists  of  a  capillary  tube  sealed  in  the  flame  and  containing  air.  This 
small  volume  of  air  becomes  more  or  less  compressed  by  the  liquid  in  the 
manometer,  owing  to  the  pressure  transmitted  to  it  from  the  ventricle.  The 
degree  of  compression  of  the  air  column  is  registered  by  the  displacement  of 
the  shadow  of  the  meniscus  of  the  liquid  column,  which  is  projected  on  to  a 
rotating  cylinder  covered  with  sensitive  paper. 

Porter  invented  a  method  with  the  same  object,  but  too  complicated  to  be 


vii  MECHANICS  OF  THE  HEAET  207 

given  here.  Both  his  results  and  those  of  Bayliss  and  Starling  confirm  the 
statement  that  the  curve  of  intraventricular  pressure  presents  a  true  systolic 
plateau  during  the  efflux  of  blood  from  the  heart.  This  important  feature 
of  the  cardiac  function  seems,  therefore,  to  be  definitely  established. 

In  perisy stole,  too,  it  is  possible  to  distinguish  two  periods ; 
the  one  shorter,  of  active  diastole,  the  other  more  prolonged,  of 
passive  diastole  or  rest  of  the  whole  heart.  During  the  former, 
pressure  falls  suddenly  both  in  ventricle  and  auricle,  and  becomes 
negative,  thus  permitting  the 
active  refilling  of  the  heart  by 
aspiration  of  blood  from  the  veins. 
During  the  second,  the  negative 
pressure  rises  again  slowly  in  the 
ventricle  and  auricle,  until  at 
the  beginning  of  presystole  it 
approximates  to  the  zero  line: 
this  represents  the  period  of 
passive  filling  of  the  heart,  caused 
by  the  vis  a  tevyo  of  the  venous 
blood  stream,  and  the  negative 
pressure  in  the  thoracic  cavity, 
when  the  experiment  is  con- 
ducted with  the  closed  thorax. 

The  elastic  ampullae  and 
sphygmoscopes  of  Chauveau  and 
Marey  are  instruments  well 
adapted  for  obtaining  tracings  of 
the  form  of  the  rapid  oscillations 
of  pressure  that  occur  within  the 

L               -,        .           .,                , .                 ,  FIG.  (58. — Ludwigs   mercury   manometer  (Xirn- 

during  the  Cardiac  Cycle,  mermann's  type).    The  float  seen  on  the  right 

tVm\7    QVA    innrtormoto    fn    rlo  consists  of  a  tine  steel  rod  terminating  at  the 

tney    aie    inadequate    DO  lower  extremity   m   a    pointed    ivory   cone, 

termine    the   absolute    value    of      wh]ch,  <^)S  into  the  column  of  mercury, 

and  at  the  upper  extremity  m  a  glass  pen 
the    intraCardiaC    preSSlire.         Ihe          tilled  with  ink,  which  traces  the  variations 

best  method  for  determining  the       %£?*« 
maximum  to  which  the  pressure 

in  the  cavities  may  rise,  and  the  minimum  to  which  it  may  fall,  is 
that  of  Goltz  and  Gaule  (1878),  which  was  also  employed  by  De 
Jager  (1883),  and  consists  in  fitting  to  the  recording  mercury 
manometer  (Fig.  68)  a  valvular  apparatus  which  closes  when  the 
pressure  falls,  and  opens  again  when  it  rises,  or  vice  versa,  so  that 
the  manometer  serves  as  a  maximum  or  minimum  manometer. 
When  connected  with  a  cavity  of  the  dog's  heart  by  means  of  an 
open  sound,  the  column  of  the  manometer  will  rise  at  each  systole 
to  a  given  maximal  height,  after  which  it  traces  a  horizontal 
line  (maximum  manometer) ;  or  falls  at  each  diastole  to  a  cer- 
tain minimum,  after  which  it  remains  stationary  (minimum 
manometer). 


208  PHYSIOLOGY  CHAP. 

The  highest  figures  for  cardiac  pressure  were  obtained  by  I)e 
Jager,  who  employed  a  maximum  manometer  and  a  sound  of  wide 
calibre,  on  large  dogs.  He  found  in  three  experimental  series : — 

T.  II.                  III. 

In  left  ventricle    ....     235  174  111  mm.  Hg. 

In  aortci 212  162  158       „ 

In  right  ventricle.         ...       28  44  72       „ 

These  values  are  probably  below  the  normal,  since  it  cannot  be 
supposed  that  the  introduction  of  a  sound  into  the  cavity  of  the 
heart  produces  no  disturbance  of  the  systolic  function. 

It  would  be  more  interesting  to  determine  the  exact  relation 
between  the  maximal  pressure  of  the  right  and  that  of  the  left 
ventricle,  since  these  must  harmonise  with  the  different  strengths 
of  the  muscular  walls  of  both  ventricles,  and  with  the  different 
resistances  which  the  two  vascular  systems  (aortic  and  pulmonary) 
present.  The  experimental  data  so  far  obtained  have  not,  how- 
ever, led  to  any  concordant  results.  On  an  average  it  may  be 
assumed  that  the  pressure  in  the  right  ventricle  and  pulmonary 
artery  is  to  that  of  the  left  ventricle  and  aorta  as  1 : 2'5,  or  1 : 3 
(Goltz  and  Gaule,  Colin,  Beutner). 

VII.  The  absolute  values  of  negative  intracardiac  pressure 
obtained  with  the  minimum  manometer  are  linked  with  the  question 
so  much  discussed  in  the  last  quarter  of  last  century,  i.e.  the 
determination  of  the  mechanical  factors  by  which  the  filling  of 
the  ventricle  during  diastole  is  effected. 

The  theory  supported  by  Harvey  and  Haller,  to  the  effect  that 
the  diastolic  filling  of  the  heart  occurs  quite  passively,  from  the 
wave  of  blood  which  rushes  from  auricle  to  ventricle  in  presy stole, 
was  for  a  long  while  accepted  almost  unanimously  by  physiologists. 
The  opposite  theory,  by  which  the  heart  acts  as  an  aspirating  pump 
in  diastole  and  as  a  pressure  pump  in  systole,  is,  however,  still 
older,  since  it  was  formulated  by  Erisistratus  and  Galen,  and 
maintained  at  a  later  period  by  Vesalius,  Bichat,  Spreiigel,  and 
Magendie,  without  indeed  finding  any  large  number  of  adherents. 

In  1871  we  revived  the  theory  of  diastolic  activity,  on  the 
strength  of  certain  rudimentary  experiments,  which  may  be 
described  as  follows  : — 

(a)  When  in  a  dog  with  opened  thorax  a  trocar  is  intro- 
duced through  the  apex  into  the  interior  of  one  of  the  ventricles, 
and  a  horizontal  glass  tube,  open  at  the  end,  is  attached  to  the 
cannula,  a  jet  of  blood  can  be  seen  in  the  tube  at  each  systole, 
which  recedes  at  each  diastole. 

(6)  If  the  pressor  effect  of  the  presystole  is  impeded  by  seizing 
the  walls  of  the  auricle  with  a  forceps,  the  diastolic  aspiration 
increases  conspicuously. 

(c)  If  in  consequence  of  vagus  excitation,  the  heart's  move- 


vii  MECHANICS  OF  THE  HEAKT  209 

ments  are  retarded,  the  diastolic  aspiration  increases  so  much  that 
the  tube  connected  with  the  ventricle  is  emptied. 

(d)  If  the  hollow  of  the  pericardial  chamber  is  filled  with  milk, 
and  connected  with  a  horizontal  glass  tube,  containing  a  fluid  to 
serve  as  index,  the  total  volume  of  the  heart  will  be  found  to 
increase  during  diastole,  while  with  gentle  stimulation  of  the 
vagus  this  diastolic  increase  of  volume  is  still  further  augmented. 
This  phenomenon  is  not  necessarily  connected  with  slowing  of  the 
heart's  action,  since  the  same  thing  can  be  seen  in  the  frog  with 
no  appreciable  changes  in  systolic  frequency.  (Coats.) 

The  conclusions  we  deduced  from  this  and  other  facts  had  the 
rare  fortune  of  being  confirmed  by  more  complete  and  decisive 
experiments.  A.  Tick  (1873)  showed  by  means  of  the  metal 
manometer,  which  he  connected  up  with  the  right  or  left  ventricle 
of  the  dog  (by  a  sound  introduced  through  the  jugular  vein  or 
carotid),  that  pressure  sinks  below  the  zero  line  during  diastole. 
Goltz  and  Gaule  (1878)  endeavoured  with  their  minimum  mano- 
meter to  determine  the  absolute  value  of  the  negative  diastolic 
pressure  with  open  thorax,  and  found  that  it  may  amount  to 
-  320  mm.  of  water  in  the  left,  and  -  25  mm.  in  the  right  ventricle, 
and  diminishes  progressively  with  the  weakening  of  systole,  i.e.  in 
proportion  as  the  systolic  evacuation  becomes  less  complete.  The 
values  obtained  by  De  Jager  by  the  same  methods  were  higher  : 
he  found  a  negative  pressure  that  may  amount  to  -  38  mm.  Hg. 
in  the  left,  and  -  6  mm.  Hg.  in  the  right  ventricle.  Values 
approximating  very  closely  to  these  were  obtained  by  other 
workers,  e.g.  Kolleston,  v.  Frey,  and  Krehl  (1890),  with  the  elastic 
manometer,  both  with  closed  and  with  open  thorax. 

It  was  Stefani,  however,  who  directly  undertook  the  task  of 
experimentally  checking,  one  by  one,  the  propositions  which 
we  had  formulated  in  1871,  and  repeated  with  certain  altera- 
tions in  1874  and  1876.  In  a  series  of  interesting  memoirs  (1877- 
1891)  he  placed  on  a  firm  experimental  basis  that  same  doctrine 
of  the  activity  of  cardiac  diastole  which  we  had  preached  for 
many  years  with  ever-growing  conviction,  adding  many  new 
arguments  in  its  favour. 

It  is  essential  to  the  comprehension  of  this  theory  to  premise  that 
the  thesis  of  active  diastole  may  be  considered  from  two  different 
points  of  view.  The  diastole  may  be  considered  active  in  a  purely 
mechanical  sense,  viz.  that  the  refilling  of  the  ventricles  during 
the  first  period  of  perisystole  is  the  effect  not  of  the  vis  a  tergo  of 
the  blood  descending  from  the  auricles  into  the  ventricles,  but  of 
the  aspiration  developed  by  the  latter  during  that  interval.  The 
expression  active  can,  however,  also  be  employed  in  a  strict 
physiological  sense,  viz.  that  the  diastole  is  controlled  and  regulated 
the  action  of  the  vagus.  Let  us  first  consider  the  mechanical 
aspect. 

VOL.  i  p 


210  PHYSIOLOGY  CHAP.  • 

We  have  already  seen  that  two  periods  can  be  detected  in  the 
course  of  a  cardiac  revolution,  during  which  the  heart  develops  a 
negative  pressure  and  exercises  aspiration  upon  the  blood  issuing f 
from  the  veins :  there  is  a  moment  of  systolic  and  a  moment  of 
diastolic  aspiration  (see  Fig.  67).  The  former  is  confined  to  the 
auricles ;  the  latter  extends  both  to  auricles  and  ventricles. 

When  systolic  aspiration  (as  in  Fredericq's  experiments  cited 
above)  takes  place  with  the  opened  thorax,  it  must  depend  on  the 
sudden  sinking  of  the  base  of  the  heart  in  the  first  period  of 
systolic  efflux,  which  increases  the  capacity  of  the  diastolic  auricle. 
This  is.  the  explanation  given  by  Purkinje  (1843),  by  Nega  (1851), 
and  more  recently  by  Chauveau  and  Lefevre,  as  well  as  Fredericq. 
This  aspiration  of  the  auricles  has  nothing  to  do  with  diastolic 
activity ;  it  is  caused  by  the  systole  of  the  ventricle,  which  works 
simultaneously  as  a  pressure  pump  against  the  arteries,  and  as  an 
aspirating  pump  against  the  auricles  and  veins. 

The  diastolic  aspiration,  on  the  contrary,  which  coincides  with 
the  first  period  of  perisystole,  and  spreads  from  the  ventricles  to  the 
auricles  and  adjacent  veins,  does  really  represent  energy  developed 
by  the  ventricles  during  diastole.  The  mechanical  effect  of 
diastole  is  indeed  very  small  as  compared  with  the  mechanical 
effect  of  systole ;  but  in  any  case  it  is  sufficient  to  defend  the 
opinion  that  the  ventricles  are  active  in  the  first  period  of  peri- 
systole,  and  dilate  by  aspiration,  not  by  the  vis  a  tergo  of  the 
blood  rushing  in  from  the  auricles.  The  little  frog  heart  is  capable 
in  its  diastolic  distension  of  overcoming  a  resistance  equal  to 
15-20  mm.  of  water  (Mosso  and  Pagliani)  ;  the  heart  of  a  dog  can 
dilate,  even  when  pressure  is  put  upon  its  outer  surface,  in  excess 
by  20-30  cm.  of  water  of  that  to  which  its  inner  surface  is  sub- 
mitted (Stefani). 

Various  hypotheses  have  been  put  forward  to  explain  the 
diastolic  aspiration,  which  may  be  rapidly  summarised : — 

(a)  The  pressure  within  the  thoracic  cavity  is  negative  even 
in  the  expiratory  position  of  the  lungs,  and  becomes  more  strongly 
negative  during  inspiration. 

As  early  as  1853  Bonders  pointed  out  the  importance  of  this 
mechanical  factor,  which  serves  to  facilitate  the  course  of  the 
blood  in  the  intrathoracic  veins  and  the  diastolic  filling  of  the 
heart  by  aspiration.  Yet  this  does  not  adequately  explain  the 
diastolic  aspiration,  which  can  be  demonstrated  even  with  the 
open  thorax.  Nor  does  it  explain  the  cardiac  aspiration  visible 
with  closed  thorax,  since  this  is  greater  in  the  left  than  in  the  right 
ventricle,  and  in  the  latter  again  than  in  the  auricles,  where  it 
should,  in  consequence  of  the  ready  extensibility  of  the  auricular 
walls,  be  greatest. 

(5)  In  1855  Briicke  revived  the  theory  of  the  auto-regulation 
gf  the  heart,  basing  it  on  the  same  arguments  as  already  brought 


vii  MECHANICS  OF  THE  HEAET  211 

forward  by  Thebesius  (1708).  According  to  this  theory  the 
coronary  arteries  empty  during  systole  and  expand  in  diastole, 
either  because  in  systole  the  orifices  of  the  coronary  vessels  are 
closed  by  the  raising  of  the  semilunar  valves  and  their  application 
to  the  walls  of  the  sinus  Valsalvae,  or  because  the  finer  ramifica- 
tions and  capillaries  of  the  coronary  vessels  are  closed  or  drawn 
together  by  the  contraction  of  the  myocardium. 

The  first  argument  was  refuted  by  Lancisi  (1728)  in  opposition 
to  Thebesius,  and  again,  with  more  cogent  reasoning,  by  Hyrtl 
against  Briicke,  and  it  is,  in  the  light  of  all  that  is  known  about 
the  mechanism  of  the  semilunar  valves,  entirely  erroneous. 
Neither  Hyrtl  nor  Ceradini,  however,  found  any  valid  objection  to 
the  second  argument,  which  is  to-day  regarded  as  established  by 
the  experiments  of  Klug  and  Rebate!,  and  the  more  recent  work 
of  Porter  and  Hyde.  Klug  succeeded  in  the  living  animal  in 
ligaturing  one  heart  in  systole  and  another  in  diastole.  On 
microscopic  examination  he  found  that  the  superficial  vessels  were 
full  of  blood  in  the  first  heart,  while  the  deeper  ones  were  almost 
empty :  in  the  second,  all  the  coronary  vessels  were  turgid. 
Rebatel,  using  Chauveau's  haemodromograph  (see  next  chapter), 
succeeded  in  obtaining  a  tracing  of  the  pressure  and  velocity  of 
flow  in  the  coronary  arteries  of  the  horse.  He  found  that  pressure 
and  velocity  increase  in  the  first  period  of  systole  ;  that  at  a 
second  period,  pressure  increases  and  velocity  decreases  until  it 
becomes  negative  (arrest  and  recession  of  blood  into  the  coronary 
vessels) ;  finally,  that  at  the  beginning  of  diastole  there  is  accelera- 
tion of  velocity  without  increase  of  pressure.  Porter  was  able  to 
convince  himself  by  an  admirable  method,  in  the  dog,  that  the 
intramuscular  branches  of  the  coronary  vessels  were  compressed 
and  emptied  by  the  contraction  of  the  myocardium,  and  that  this 
systolic  evacuation  assisted  the  streaming  of  the  blood  through  the 
walls  of  the  heart  when  the  myocardium  relaxed,  owing  to  the 
diminished  resistance  offered  by  the  slack  and  empty  vessels  to  the 
blood-stream.  Lastly,  Hyde  studied  the  effects  of  the  various 
distensions  of  the  ventricular  cavities  on  the  isolated  cat's  heart, 
by  suffusing  blood  through  the  coronary  vessels  at  constant 
pressure.  He  determined  that  whether  the  heart  was  at  rest  or 
beating,  the  flow  of  blood  diminished  when  the  heart  was  more 
extended,  i.e.  when  circulation  in  the  coronary  arteries  was 
impeded. 

But  even  if  the  automatic  regulation  of  the  heart,  in  so  far  as 
systole  impedes  the  circulation  in  the  coronary  arteries  by  com- 
pressing them,  while  diastole  facilitates  the  filling  of  the  coronaries, 
be  accepted,  it  does  not  necessarily  follow,  as  assumed  by  Briicke, 
that  there  is  in  diastole  a  kind  of  erection  of  the  cardiac  walls 
which  tends  to  produce  a  negative  pressure  in  the  cavity,  and  to 
facilitate  its  filling.  It  is  true  that  Bonders  and  Albini  claim, 


212  PHYSIOLOGY  CHAP. 

with  the  help  of  a  manometer  communicating  with  a  cavity  in  the 
dead  heart,  to  have  observed  a  diminution  of  pressure,  so  soon  as 
they  injected  the  walls  of  the  heart  from  the  coronary  artery ;  but 
Oehl,  on  repeating  the  experiment,  found  exactly  the  contrary,  i.e. 
increase  of  pressure  within  the  heart,  so  soon  as  the  pressure  was 
strongly  augmented  in  the  coronary  vessels. 

This  contradiction  between  the  results  of  such  experienced 
experimenters  shows,  without  reference  to  other  arguments  that 
might  be  brought  forward,  and  have  been  adduced  by  Oehl,  that 
Briicke's  theory  is  quite  inadequate  to  explain  diastolic  aspiration. 

(c)  Gaule  (1886)  suggested  'that  the  negative  pressure  in  the 
ventricle,  which  he  determined  with  Goltz  by  means  of  a  minimum 
manometer,  depended  on  the  dilatation  of  the  aortic  orifice  after 
closure  of  the  semilunar  valves  at  the  commencement  of  diastole. 
Since  the  aorta  is  connected  with  the  fibrous  ring  from  which  the 
muscle  fibres  of  the  ventricle  originate,  it  follows  that  the  ventri- 
cular cavity  must  dilate  at  the  moment  when  the  ring  becomes 
distended,  producing  a  negative  pressure.  Both  Minck  (1890)  and 
Krehl  (1891)  proposed  this  hypothesis. 

But  even  if  it  is  undeniable  that  when  the  aortic  orifice  dilates, 
the  conus  arteriosus  which  lies  below,  and  is  in  a  certain  sense  one 
with  it,  dilates  also,  it  does  not  follow  that  this  condition  occurs  at 
the  beginning  of  diastole,  and  can  explain  the  diastolic  aspiration. 
The  maximum  of  pressure  and  dilatation  in  the  bulbus  aortae 
must  obviously  be  reached  during  the  systolic  efflux,  and  not  at 
the  commencement  of  diastole.  "  At  the  first  outpouring  of  the 
systolic  stream,"  as  Ceradini  says,  "  the  bulbous  portion  of  the 
artery  (aorta  or  pulmonary)  dilates,  so  that  each  of  its  diameters 
increases  by  about  one-fifth  ;  the  walls  of  the  sinus  Valsalvae  are 
better  able  to  resist  the  impact,  yet  they,  too,  show  a  very  consider- 
able dilatation,  owing  to  the  distension  of  the  valvular  membranes, 
whose  free  borders  become  straight  at  the  first  onset." 

At  the  commencement  of  diastole,  on  the  other  hand,  the 
valves  are  already  closed  and  bulge  towards  the  conus  arteriosus, 
so  as  to  diminish  its  capacity,  presenting  with  their  united  margins 
'the  figure  of  the  sides  of  a  tetrahedron,  the  apex  of  which,  built 
up  of  the  three  coincident  corpora  Arantii,  falls  on  its  vertical 
axis,  and  is  inverted  downward  towards  the  hollow  of  the 
conus  arteriosus.  "The  insertion  of  the  valvular  borders,"  says 
Ceradini,  "  are  externally  recognisable  at  the  points  of  contact  of 
the  ellipsoid  formed  by  the  sinus  Valsalvae,  by  a  conspicuous 
depression,  which  is  visible  at  the  arterial  wall  at  the  first  onset  of 
diastole,  in  consequence  of  the  sudden  distension  of  the  semilunar 
membranes." 

Gaule's  explanation  accordingly  fails  to  explain  the  diastolic 
aspiration. 

(d}  The  oldest  hypothesis  in  explanation  of  the  active  diastole 


vii  MECHANICS  OF  THE  HEAET  213 

is  that  of  Galen,  who  distinguished  in  the  heart  predominatingly 
transverse,  and  predominatingly  longitudinal  fibres.  In  systole 
the  former  contract,  and  the  cavities  of  the  heart  are  restricted ; 
in  diastole  the  latter  contract,  and  the  cavities  are  dilated. 
Vesalius  assumed  much  the  same  position,  which  had  many 
adherents  both  before  and  after  Harvey,  who  denied  that  there  was 
diastolic  activity.  In  1861  it  was  revived  (with  slight  modifica- 
tions) by  Spring.  He  supposed  that  the  more  or  less  longitudinal 
fibres  of  the  heart  contracted  somewhat  before  the  transverse,  thus 
producing  an  active  dilatation  of  the  ventricular  cavities  before 
the  commencement  of  systole  proper.  This  theory  is,  however, 
put  out  of  court  by  the  fact  that  aspiration  is  determined  not  at 
the  pre-systolic  but  at  the  post-systolic  moment. 

Brachet  (1815)  maintained  that  active  diastole  depended  on 
hypothetical  radial  fibres,  coursing  from  endocardium  to  peri- 
cardium, which  he  believed  himself  able  to  demonstrate  on  the 
heart  of  man,  horse,  and  ox.  According  to  this  author,  the  walls 
of  the  heart  exhibit  a  considerable  thickening  in  systole ;  in 
diastole  the  radial  transverse  fibres  contract  and  reduce  the 
diameter  of  the  walls  of  the  heart,  thus  augmenting  its  capacity. 
Most  French  writers  of  the  first  half  of  last  century,  e.g.  Filhos 
(1855),  Choriol  (1841),  upheld  this  view,  which,  however,  was 
strongly  disputed  by  Parchappe  and  Berard.  In  order  to  prove 
this  position  it  would  be  necessary  to  show  that  the  two  kinds  of 
fibres  in  cardiac  muscle  contracted  successively  and  not  simul- 
taneously, as  we  must  assume. 

In  a  corrected  and  amended  form  the  hypothesis  of  Galen,  of 
Brachet,  and  of  Spring  was  revived  by  Krehl  (1891).  He  assumes 
an  unequal  (i.e.  a  non-sychronous)  relaxation  of  the  different 
muscular  layers  of  the  heart,  and  held  that  the  expulsor  muscle 
(intermediate  layer  of  the  left  ventricle)  relaxed  earlier  than  the 
longitudinal  fibres  of  the  internal  layer,  so  that  the  latter,  being 
no  longer  compressed,  enabled  the  walls  of  the  ventricle  to  move 
apart.  He  founds  his  position  upon  the  experiment  of  Eoy  (1890), 
who  succeeded  in  obtaining  simultaneous  tracings  of  the  contraction 
of  the  walls  of  the  heart,  and  of  the  papillary  muscles,  and  demon- 
strated that  these  last  contract  later  and  relax  earlier.  This 
fact,  however,  contradicts  Krehl's  view,  according  to  which  the 
papillary  muscles  relax  later  than  the  walls  of  the  ventricle. 
Among  Krehl's  various  hypotheses  this  appears  to  us  the  least 
acceptable. 

(e)  The  most  universally  accepted  view  of  diastolic  aspiration 
is  that  it  depends  on  the  elastic  reaction  of  the  myocardium, 
thrown  into  tension  at  systole.  This  is  the  theory  which  was 
clearly  expressed  in  1838  by  Magendie,  when  he  compared  diastole 
to  the  dilatation  of  a  rubber  tube  when  released  i'rom  compression. 
L,  Fick  (1849)  was  the  first  to  prove  this  on  the  dead  heart  in 


214  PHYSIOLOGY  CHAP. 

which  he  imitated  systole  by  compressing  it  with  his  hand,  and 
diastole  by  simply  releasing  it.  On  sinking  the  heart  in  a  vessel 
of  water,  he  was  able  at  each  compression  to  drive  a  jet  of  fluid 
through  the  arteries,  a  proof  that,  after  releasing  the  ventricles, 
the  internal  cavity  distended  and  filled  with  water.  It  was 
objected  to  this  experiment  that  the  phenomenon  might  be  due 
to  cadaveric  rigidity  of  the  heart :  Goltz  and  Gaule,  however, 
regarded  the  elastic  reaction  of  the  heart  at  the  commencement 
of  diastole  as  proved  by  their  experiments  with  the  minimum 
manometer. 

The  same  view  was  taken  by  De  Jager,  who  met  every  con- 
ceivable objection  to  the  theory  that  the  filling  of  the  heart  at  the 
commencement  of  diastole  depended  not  on  the  vis  a  tergo  of  the 
blood,  but  on  the  elastic  reaction  of  the  heart's  walls,  by  the  fact 
that,  after  opening  the  thorax,  pressure  is  at  zero  in  the  cavity  of 
the  right  auricle  and  adjacent  vein.  This  one  fact  is  sufficient 
to  establish  the  doctrine  of  diastolic  activity  in  the  mechanical 
sense. 

But  in  this  connection  arises  the  (juestion  of  the  origin  of  this 
elastic  reaction  at  the  commencement  of  diastole.  Is  it  dependent 
on  cardiac  muscle  properly  so-called,  or  on  the  elastic  tissue 
implanted  in  the  walls  of  the  heart  ?  Certain  authors  subscribe  in 
virtue  of  quite  independent  arguments  to  the  former  of  these 
theories,  admitting  a  possibility  of  an  active  lengthening  of  the 
muscular  fibres  of  the  myocardium.  The  first  to  express  this 
view  was  the  English  physiologist  Carpenter,  who,  at  the  end  of 
1855,  maintained  that  the  active  force  which  causes  the  heart  to 
dilate  must  originate  in  the  myocardium  proper.  He  propounded 
the  hypothesis  that  just  as  active  muscular  contraction,  which 
causes  the  muscle  to  shorten,  depends  on  the  attraction  of  the 
particles  of  which  that  muscle  is  formed,  so  the  reciprocal  re- 
pulsion of  those  same  particles  must  produce  the  active  elongation 
of  the  muscle  fibre. 

In  1871,  not  being  aware  of  Carpenter's  hypothesis,  we  brought 
forward  another,  essentially  similar  to  it,  but  differently  expressed. 
We  suggested  that  the  contraction  and  subsequent  expansion  of 
the  myocardium  might  be  determined  by  two  antagonistic 
physiological  processes,  so  that  the  cardiac  diastole  would,  like 
the  systole,  be  an  active  movement.  At  a  later  time  this  hypo- 
thesis was  taken  up  and  elaborated  by  Stefani  (infra). 

Lastly,  mention  must  be  made  of  Albrecht,  who  has  recently 
(1903)  published  a  valuable  study  on  the  myocardium.  He,  too, 
considers  diastole  to  be  an  active  physiological  process,  on  the  ground 
of  Verworn's  theory  of  the  general  physiology  of  muscle.  Accord- 
ing to  Verworn  the  expansive  phase  of  the  mechanical  response 
of  muscle  is  active,  and  is  determined  by  the  tendency  of  the  aniso- 
tropous  substance,  saturated  during  the  contractive  phase  by  the 


vii  MECHANICS  OF  THE  HEAHT  215 

katabolic  products,  to  assimilate  oxygen  and  nutrient  juices  from 
the  environment.  For  this  purpose  the  anisotropous  substance  seeks 
to  acquire  the  largest  possible  superficies,  i.e.  it  expands.  Yerworn 
does  not  deny  that  this  expansive  movement  (i.e.  relaxation)  is 
assisted  by  numerous  extrinsic  factors,  e.g.  the  tension  of  tendons 
and  fascia,  etc.,  but  he  still  attributes  a  not  inconsiderable  function 
to  the  expansive  activity  proper  of  the  muscle  fibres.  Albrecht 
extended  to  the  heart  the  idea  which  Yerworn  had  formulated  for 
muscles  in  general.  He  accordingly  defines  diastolic  activity  as  a 
functional  necessity  of  recuperation. 

Other  authors,  on  the  contrary,  ascribe  the  active  character  of 
diastole  to  the  elastic  tissue  contained  in  the  myocardium.  Krehl 
appears  to  have  adopted  this  hypothesis.  He  holds  that  there  are 
many  elastic  fibres  beneath  the  endocardium,  surrouuding  the 
muscle  bundles  of  the  internal  layers,  which  may  be  thrown  into 
tension  during  systole,  and  react  in  diastole  by  dilating  the 
cavities  of  the  heart.  The  elastic  lamellae  which  extend  from  the 
semilunar  valves  passing  under  the  origin  of  the  aorta  into  the 
interior  of  the  muscles  may  produce  the  same  effect.  Lastly,  he 
believes  that  the  root  of  the  aorta,  deeply  implanted,  and  always 
distended  under  high  pressure  during  the  energetic  systolic 
diminution  of  the  base  of  the  heart,  must  be  deformed ;  so  that  at 
the  commencement  of  diastole,  when  it  recovers  its  position  of 
equilibrium,  the  pressure  must  involve  .a  distension  of  the  soft 
muscles.  This  last  idea  is  a  new  form  of  Gaule's  hypothesis,  as 
already  refuted.  In  any  case,  Krehl's  propositions,  as  a  whole, 
leave  us  uncertain  whether  the  dilator  reaction  of  the  heart,  at 
the  commencement  of  diastole,  is  to  be  ascribed  to  the  elastic 
tissue  or  to  the  cardiac  muscle.  The  former  is,  however,  absolutely 
put  out  of  court  by  certain  very  important  facts  adduced  by 
Stefani,  which  go  to  determine  the  physiological  character  of  the 
active  diastole. 

VIII.  In  a  previous  paragraph  we  referred  to  the  changes  in 
total  volume  of  the  heart,  during  the  several  periods  of  its  activity. 
We  said  that  it  diminished  during  systole,  at  the  termination  of 
which  meiocardia  occurs,  i.e.  the  maximal  diminution  of  the  heart's 
volume ;  and  that  it  increases  during  perisystole  until  it  attains 
the  maximal  volume,  or  auxocardia,  at  the  commencement  of 
presystole. 

After  our  first  experiments  in  1871  (in  which,  to  estimate 
the  changes  in  volume  of  the  heart,  we  employed  the  pericardial 
cavity  filled  with  milk)  Franck  and  Stefani  (1877)  were  the  first 
who  adopted  the  method  of  the  pericardial  fistula  for  curarised 
dogs,  kept  alive  by  artificial  respiration — tracings  of  the  oscillations 
of  the  total  volume  of  the  heart  (cardiac  plethysmogram)  being 
recorded  on  a  rotating  drum.  This  is  easy  enough  with  simple  air 
transmission,  i.e.  by  connecting  up  the  cannula  applied  to  the 


216 


PHYSIOLOGY 


CHAP. 


pericardium  with  a  tambour  and  writing  lever,  artificial  respira- 
tion being  temporarily  suspended. 

The    plethysmograms    obtained    by    this    method    give    an 
approximate  picture  of  the  quantity  of  blood   with  which  the 


Fio.  69.— Cardiac  plethysmograms.  (Stefani.)  o,  b,  Descending  portion,  coinciding  with  systolic 
outflow  ;  b,  c,  rapidly  ascending  portion,  coinciding  with  active  diastolic  influx ;  c,  a,  nlowly 
ascending  portion,  coinciding  with  passive  diastolic  influx  ;  d,  notches,  which  nearly  always 
occur  on  the  ascending  shoulder. 

heart  is  charged,  or  which  it  discharges  at  the  different  periods  of 
its  cycle,  and  consequently  of  the  systolic  diminution,  and  peri- 
systolic  amplitude  of  the  ventricular  cavity. 

As  appears  from  the  tracings  in  Fig.  69  we  can  distinguish : — 

(a)  A  rapidly  descending  line  which  coincides  with  the  period 
of  systolic  evacuation. 

(ft)  A  rapidly  ascending  line  (in  which  there  is  invariably  a 
notch)  corresponding  with  the  period  of  active  diastole. 

(c)  A  slowly  ascending  line  (sometimes  horizontal  or  even 
slightly  descending  as  shown  in  Fig.  70),  which  corresponds  to  the 
time  of  passive  diastole  and  presystole. 

It  is  obvious  that  neither  the  period  of  presystole  nor  the 
succeeding  interval  of  tension  or  latent  systole,  during  which  the 
total  volume  of  the  heart  undergoes  no  important  modification,  can 
be  distinctly  shown  in  cardiac  plethysmograms.  Since  in  the 


FIG.  70.— Cardiac  plethysmograms,  in  which  the  line  •:,  a  of  passive  refill  is  descending  or 
almost  horizontal. 

third  period  of  the  plethysmogram  there  may  be  a  slight  augmenta- 
tion of  cardiac  volume,  or  it  may  be  stationary,  or  diminish,  the 
deduction  of  Stefani  seems  valid,  to  the  effect  that  "  the  venous 
current  (in  consequence  particularly  of  presystole)  must  in  the 
first  case  suffer  a  simple  retardation,  in  the  second  an  arrest,  in 


vii  MECHANICS  OF  THE  HEART  217 

the  third  a  reflux."     The  most  important  results  which  Stefani 

obtained  from  analysis  of  cardiac  plethysmograms  are  as  follows : — 

(a)  Their  magnitude  varies  considerably  not  merely  in  different 

animals,  but  also  in   the  same  animal,  showing  that  the  heart, 


Fie.  71.  — A,  Plethysmogram  obtained  under  normal  renditions  ;  B,  Plethysmogram  from  same 
dog,  during  dyspnoeie  excitation  of  vagus. 

under  different  circumstances,  is  able  more  or  less  completely  to 
nil  and  empty  itself  of  blood,  "  so  that  it  may  assume  a  volume 
considerably  greater  than  that  attained  in  the  preceding  cycles, 
independent  of  any  modification  in  the  frequency  of  the  beat" 
(This  comes  out  clearly  in  Figs.  69,  70,  71.) 

(&)  There  is  no  perceptible  difference  in  the  duration  and  form 
of  the  two  first  periods  of  the  plethysniogram  (line  of  systolic 


FIG.  72.— Plethysmogram  showing  augmentation  of  cardiac  volume  during  excitation 
of  left  vagus. 

evacuation  and  active  diastolic  refill)  with  changes  in  frequency 
of  the  heart's  beat.  It  is  only  the  third  period  (of  slow  passive 
refilling)  that  varies  in  duration  and  form  with  the  acceleration 
or  retardation  of  the  cycle.  (This  is  demonstrated  in  the  tracings 
of  Figs.  71,  72,  73.) 


218 


PHYSIOLOGY 


CHAP. 


From  this  Stefani  draws  the  logical  conclusion  that  both  the 
first  and  second  periods  of  the  plethysmograrn  are  the  effect  of 
physiological  activity — while  only  the  third  can  be  regarded  as  the 
effect  of  repose  of  the  heart. 


Fi<;.  73.— Pli'thysmogram  showing  that  stimulation  of  oii»>  vagus  by  strong  induction  currents 
has  no  e  fleet  on  systolic  evacuation,  but  conspicuously  increases  the  period  of  passive  refill. 

(c]  If  the  vagus  be  excited,  either  directly  or  by  cessation  of 
artificial  respiration  (which  has  the  effect  of  increasing  the  venosity 
of  the  blood),  profound  changes  appear  in  the  cardiac  -plethys- 
inograms,  varying  in  form  according  to  the  degree  of  excitation 
and  the  excitability  of  the  nerve,  but  all  having  this  in  common 
that  the  ascending  line  of  the  diastolic  refill  has  a  considerable 
upward  lift,  which  signifies  that  the  heart  acquires  a  greater 
volume.  (Tracings  of  Figs.  71,  72,  73,  74,  75.) 

This  phenomenon  cannot  be  dependent  on  the  slowing  or 
suspension  of  the  beats  of  the  heart,  because  on  the  one  hand  the 
increase  of  volume  occurs  rapidly  and  in  a  degree  which  far  exceeds 
the  normal,  and  on  the  other  there  is  a  marked  demarcation 
between  that  part  of  the  line  of  refill  which  corresponds  with  active 
and  that  which  corresponds  with  passive  diastole ;  and  finally 
because  the  heart  is  able  on  excitation  of  the  vagus  to  attain  its 
maximum  volume  before  the  venous  pressure  has  had  time  to  rise 

to   any   considerable 
extent  (Fig.  76). 

Stefani  considers 
that  these  facts  con- 
firm the  doctrine 
we  have  maintained 
since  1871,  to  the 

Fio.  74.— Plethysrnogram  in  which  gentle  excitation  of  one  vagus    effect   that  the  VagUS 
(at  +)  makes  systolic  evacuation  incomplete,  while  it  increases     •  rlioofrJin    narxro 

diastolic  refill.  1S    a    OUdSlOllC    nerve, 

in    the    sense    that 

"  it  actively  provokes  increase  of  volume  in  the  heart,  by  modify- 
ing the  physiological  condition  of  the  cardiac  muscles." 

This  same  theory  of  the  mode  of  action  of  the  vagus  upon  the 
heart  (to  be  discussed  in  detail  in  the  next  chapter)  was  successively 
put  forward  by  Eossbach  (1882),  Heidenhain  (1882),  Williams 
(1887),  Tigerstedt  and  Johannssohn  (1889),  and  also  by  Francois- 


VII 


MECHANICS  OF  THE  HEAET 


219 


FIG.  T5. — Plethysmogram  showing  that  strong  ex- 
citation of  one  vagus  (at  -j-)  exaggerates  effect 
shown  in  preceding  figure. 


Franck  (1891),  who  in   1877  had   pronounced   in   precisely   the 
opposite  sense. 

It  thus  became  necessary  to  determine  more  exactly  the  nature 
of  the  action  of  the  vagus,  in  so  far  as  it  is  a  diastolic  nerve,  capable, 
i.e.,  of  modifying  the  internal 
physiological  state  of  the 
cardiac  muscles.  With  this 
object,  Stefani  undertook  to 
measure  the  pressure  that 
must  be  exerted  on  the  outer 
surface  of  the  heart  in  order 
to  arrest  the  circulation  of 
the  blood.  This  he  compared 
with  the  pressure  simultane- 
ously exerted  upon  its  in- 
ternal surface,  and  noted  the 
changes  in  the  difference  between  the  two  pressures,  according  as 
the  vagus  was  excited  or  paralysed.  From  this  ingenious  and 
original  research  Stefani  obtained  most  important  results,  which 
we  may  summarise  in  a  few  words. 

A  pericardial  fistula  was  made  on  a  dog,  the  cavity  being 
connected  by  a  T-shaped  tube,  on  the  one  hand  with  a  pressure 
bottle  filled  with  1  per  cent  solution  of  NaCl,  on  the  other  with 
a  mercury  manometer.  When  the  fluid  is  made  to  descend  into 
the  cavity  of  the  pericardium,  the  manometer  measures  the  pressure 
exerted  on  the  outside  of  the  heart.  Another  manometer,  in  which 

an  alkaline,  anti-coagulant 
solution  is  substituted  for 
mercury,  is  connected  with 
a  glass  tube  introduced  in- 
to the  vena  cave  superior, 
in  order  to  measure  the 


venous  pressure  acting 
upon  the  internal  surface 
of  the  heart.  A  third 
mercury  manometer  can 
be  connected  with  the 
carotid  in  order  to  rneas- 

Fio.  76. — The  upper  curve  represents  the  venous  pressure,  1  .    , 

the  lower  the  plethysmograrn.     At  «,  a  (the  corre-  U1'6  the  arterial  pressure, 
spending  points  on  either  curve)  one  vagus  was  strongly  j      T,vr.^nv<-  4nil  w:<-  U  fV,a 

excited.    The  two  curves  show  that  the  augmentation  ^n  proportion  Wltll  bllt 

of  cardiac  volume  corresponds  to  a  slight  fall  of  venous  increase        of        "Pericardial 
blood  pressure., 

pressure,  the  venous  pres- 
sure increases  owing  to  the  obstruction  of  the  flow  to  the  heart, 
while  arterial  pressure  diminishes  owing  to  the  diminished  out- 
put from  the  heart.  When  the  pericardial  pressure  is  so  high 
that  it  completely  inhibits  the  flow  of  blood  to  the  heart  and 
circulation  is  arrested,  the  arterial  pressure  rises  to  15-20  min.  Hg 


220 


PHYSIOLOGY 


CHAP. 


and  the  venous  pressure  to  12-18  cm.  H20.  If  one  vagus  is 
stimulated  by  an  induction  current  at  the  moment  at  which 
circulation  ceases,  the  interesting  phenomenon  of  a  rise  in  ar- 
terial pressure  may  be  observed,  and  cannot  be  explained  other- 
wise than  by  admitting  with  Stefani  that  the  heart  is  capable, 
under  vagus  stimulation,  of  charging  itself  with  blood,  even  against 
the  pericardial  pressure,  which  previously  impeded  this  loading. 
The  vagus  is  thus  able  to  excite  active  dilatation  of  the  heart. 

Stefani  applied  the  term  diastolic  pressure  to  that  exerted  by 
the  heart  in  diastole  upon  the  surrounding  fluid  of  the  pericardium, 
by  which  it  overcomes  the  resistance,  distends  its  cavities,  and 
permits  the  blood  to  penetrate  it.  He  measured  this  diastolic 
pressure  in  eight  dogs,  determining  the  difference  between  the 
pressure  in  the  pericardial  cavity  and  in  the  vena  cava.  The 
results  are  as  follows  :  — 


At  the  moment  of  Arrested  Circulation. 

No.  of 

Animal. 

1 

Pressure  in  Pericardium. 

Pressure  in  Vena  Cava. 

Diastolic  Pressure. 

1 

35  cm.  H 

,0 

10  cm.  H.,0 

25  cm.  H.,0 

2 

20    ,, 

6 

14 

j 

3 

40    „ 

8 

32 

4 

27    „ 

13 

14 

j 

r} 

27    ,, 

8 

19 

5 

6 

27    ,, 

13 

14 

, 

/ 

25    „ 

14 

11 

) 

1           8 

26    „ 

12 

14 

' 

It  appears  from  these  figures  that  in  ordinary  diastole  the 
heart  develops  a  pressure  upon  the  pericardial  fluid  which  is  capable 
on  an  average  of  supporting  a  column  of  water  of  19  cm.  This 
result  harmonises  well  with  that  obtained  by  the  minimum 
manometer  of  Goltz  and  Gaule  as  described  above. 

On  measuring  the  pericardial  pressure  capable  of  arresting  the 
circulation,  before  and  comparatively  soon  after  section  of  the  vagi, 
Stefani  obtained  the  following  results  on  five  dogs :— 


.Pericardical  Pressure  able  to  Arrest  Circulation. 

No.  of 
Animal. 

Difference. 

Before  Section  of  Vagi. 

After  Section  of  Vagi. 

1 

35  cm.  H20 

20  cm.  HoO 

15  cm.  H20 

2 

26    „      „ 

16    ,,       „ 

10    „      „ 

3 

21     „       „ 

12    „      „ 

9    „      „ 

4 

24    „       „ 

13    „      „ 

11    p,      „ 

5 

23    „       „ 

13    „      „ 

10    ,,      „ 

VII 


MECHANICS  OF  THE  HEAET 


221 


Diastolic  pressure  is  accordingly  reduced  after  division  of  the 
vagi  to  an  average  of  11  cm.  H20,  i.e.  to  a  value  little  more  than 
half  of  that  developed  with  intact  vagi,  which  confirms  the  diastolic 
or  dilator  action  of  the  vagi  upon  cardiac  muscle. 

If  the  vagus  is  excited  after  bringing  the  circulation  to  a 
standstill  by  pericardial  pressure,  the  manometer  in  connection 
with  the  pericardial  cavity  shows  a  rise  of  pressure  which  soon  falls 
again  when  stimulation  ceases.  If  these  oscillations  of  the  mano- 
meter be  recorded  on  a  rotating  cylinder,  the  following  tracing 
(Fig.  77)  is  obtained,  which  is  a  new  and  direct  proof  that  the 
degree  of  diastolic  dilatation  is  regulated  by  the  vagus. 

Lastly,  in  order  better  to  control  the  theory  of  diastolic  activity, 
Stefani  successfully  employed  certain  poisons  (atropine,  digitaline, 
and  strychnine),  measuring  the  diastolic  pressure  before  and  after 
injection  of  the  drug,  and  before  and  after  section  of  the  vagi. 
He  came,  in  a  few  words,  to  the  following  conclusions :  that 


FIG.  77. — The  recording  mercury  manometer  is  connected  with  the  pericardial  cavity.  Show 
disappearance  of  plethysmographic  oscillations  in  the  heart,  in  consequence  of  hydrostatic 
pressure  exerted  within  pericardium.  The  vagus  was  stimulated  in  the  neck  at  + ,  slightly  at 
first,  afterwards  more  strongly.  —  marks  close  of  excitation.  During  stimulation  the  heart 
dilates,  and  resumes  its  original  volume  at  the  close  of  excitation.  (Stefani.) 

atropine  lowers  the  diastolic  pressure  because  it  paralyses  the 
dilator  action  of  the  vagi,  and  that  digitaline  and  strychnine  increase 
the  diastolic  pressure  because  they  act  directly  upon  the  cardiac 
muscle,  and  render  it  capable  of  active  dilatation  in  excess  of  the 
normal. 

Until  these  important  facts  determined  by  Stefani  are  con- 
tradicted or  shown  to  be  fallacies,  we  shall  continue  to  regard  the 
theory  of  diastolic  activity  (which  we  formulated  in  1871)  to  be 
well  founded,  both  from  a  purely  mechanical  and  from  a  physio- 
logical point  of  view. 

In  the  ninth  chapter  we  shall  discuss  certain  experimental 
data  which  enable  us  to  determine,  up  to  a  certain  point,  the 
nature  of  the  internal  process  by  which  the  vagus  develops  and 
regulates  the  activity  of  the  diastole, 

IX.  After  developing  the  mechanism  of  the  systolic  evacuation 
and  diastolic  refill  of  the  heart  it  is  easy  to  deal  with  the  question 
of  the  cardiac  beat  or  pulse,  which,  like  the  heart-sounds,  con- 
stitutes an  important  external  sign  in  the  investigation  of  this 


222  PHYSIOLOGY  CHAP. 

organ  in  man  and  in  intact  animals.  It  consists  in  a  rhythmical 
elevation  of  the  intercostal  spaces  corresponding  with  the  peri- 
cardial  region  to  the  left  of  the  sternum.  The  impact  is  generally 
supposed  to  be  greatest  at  the  level  of  the  fifth  intercostal  space,  a 
little  within  the  mamillary  line,  where  the  apex  of  the  heart  lies 
normally  ;  but  from  a  series  of  careful  investigations  by  Mariannini 
and  Narnias  (1882)  it  appears,  on  the  contrary,  that  the  point 
at  which  the  beat  of  the  heart  is  normally  strongest  corresponds 
more  frequently  (in  67  per  cent)  with  the  fourth  than  with  the 
fifth  intercostal  space,  in  the  supine  horizontal  position.  It  is 
usually  perceived  by  palpation,  but  in  thin  persons  with  large 
intercostal  spaces  it  is  visible  to  the  eye. 

Harvey  was  the  first  to  point  out  that  the  cardiac  beat 
occurred  during  systole.  His  theory  is  the  more  valuable,  inas- 
much as  he  had  the  opportunity  of  directly  observing  the  beats  of 
the  heart  on  Viscount  Montgomery,  who  had  lost  part .  of  his 
thoracic  wall  through  an  accident,  so  that  the  exposed  heart  was 
visible  (Exercitatio  de  generatione  animalium,  lii.). 

This  generally  accepted  doctrine,  which  has  received  ample 
confirmation  from  modern  researches  with  the  graphic  method,  was 
at  one  time  contradicted,  on  the  strength  of  fallacious  observations 
in  which  the  ictus  cordis  was  regarded  as  the  effect  of  the  sudden 
dilatation  of  the  ventricles  at  the  moment  of  presystole.  Corrigan, 
Stokes,  Pigeaux,  Burdach  (1832),  Beau  (1835),  Baccelli  (1859), 
successively  held  a  brief  for  this  theory,  which  owed  its  success,  as 
Marey  remarked,  "  a  ce  qu'elle  etait  simple  et  logiquement  deMuite." 

The  first  promoters  of  this  theory,  Corrigan  and  Stokes,  ad- 
mitted their  error,  and  that  it  is  still  perpetuated  by  the  Italian 
clinician  Baccelli  is  doubtless  the  result  of  an  ambiguity.  At  the 
Kome  Congress  in  1894  he  maintained  that  the  impact  of  the 
heart  coincides  with  the  moment  immediately  preceding  systole. 
It  is  obvious  that  by  systole  he  means  the  period  of  evacuation  or 
ventricular  efflux,  as  was  always  understood  by  physiologists  as 
well  as  clinicians,  prior  to  the  introduction  of  the  graphic  method. 
But  since  it  is  now  well  established  that  the  efflux  is  preceded  by 
a  period  of  tension  or  of  latent  systole,  which  lasts  from  0*10  to  0*08", 
it  is  clear  that  this  must  be  the  moment  with  which,  according  to 
Baccelli,  the  impact  of  the  heart  coincides.  We  are  completely  at 
one  with  this  opinion,  provided  it  be  understood  in  the  sense  that 
the  displacement  of  the  thoracic  wall  reaches  its  greatest  height 
during  that  period.  It  agrees,  in  fact,  perfectly  with  what  we 
learn  from  the  cardiogram. 

The  method  now  generally  adopted  by  physiologist*)  and  clinicians  in 
recording  the  tracings  of  the  cardiac  beat  (cardiogram)  is  that  of  tambours 
with  an  elastic  membrane  and  air  transmission.  Hiirthle,  in  1892,  made  an 
interesting  control  research  with  the  different  models  of  cardiographs  as 
employed  by  various  workers.  This  was  the  more  useful  since  we  should, 


vii  MECHANICS  OF  THE  HEART  223 

a  priori,  expect  a  certain  number  of  tlie  various  characteristics  found  by 
different  authors  in  the  cardiograms  of  healthy  individuals,  to  be  due  to  the 
method  or  rather  to  the  instruments  employed.  Hiirthle  performed  a  double 
series  of  experiments.  In  the  first  place,  with  the  tambours  of  Marey,  Knoll, 
and  Grunmach,  lie  recorded  an  identical  impulse,  mechanically  produced. 
Then  with  the  same  tambours  lie  successively  recorded  the  cardiograms  of  one 
healthy  individual.  The  result  of  his  experiments  showed  that  while  Marey's 
tambour  was  not  wholly  free  from  error  it  recorded  the  impulses  in  such  a 
way  as  to  reproduce  their  characteristics  accurately.  The  cardiographs 
invented  by  Knoll  and  Gnmmach,  on  the  other  hand,  were  very  fallacious. 

The  following  tracing  (Fig.  78),  obtained  by  Frangois-Franck 
from  a  woman  suffering  from  ectopia  cordis  congenita,  is  convincing 
since  in  this  case  the  heart,  having  dropped  down  through  an 
abnormal  opening  in  the  diaphragm,  beat  beneath  the  skin  in  the 
linea  alba  of  the  epigastrium.  It  is  clear  that  the  rhythmical 
elevation  determined  by  the  ventricular  systole  commences  exactly 
at  the  close  of  presystole. 


FIG.  78.  —  o.d,  Cardiograms  of  right  auricle  ;  r.d,  cardiograms  of  right  ventricle,  recorded 
simultaneously  by  two  separate  explorers  with  writing  levers.     (Francois- Franck.) 

No  less  convincing  are  the  cardiograms  obtained  from  man 
under  normal  topographical  conditions  of  the  heart,  which  are 
recorded  simultaneously  by  an  electric  signal  at  the  precise 
moment  at  which  the  first  and  second  sounds  are  first  heard.  We 
have  shown  that  the  first  sound  is  concomitant  with  systole,  and 
any  one  who  questions  whether  it  begins  at  the  moment  of 
tension,  i.e.  prior  to  the  ventricular  efflux,  need  only  study  the 
tracing  obtained  by  Marey  from  the  horse  with  a  cardiographic 
sound  introduced  into  the  right  ventricle  (Fig.  79). 

Starting  from  this  well-established  fact,  the  cardiograms  of 
the  heart -beat  (Fig.  80)  which  Edgren  obtained  from  his 
cardiograph,  used  simultaneously  with  the  stethoscope,  have 
the  same  value  and  lead  to  the  same  conclusions  as  the  fore- 
going tracings  of  Francois- Franck. 

Since  the  cardiac  pulse  is  proved  to  be  initiated  in  the  rapidly 
ascending  movement  before  the  intraventricular  tension  has  suc- 
ceeded in  opening  the  semilunar  valves,  all  those  hypotheses  are 
necessarily  discredited  which  seek  to  explain  this  phenomenon. 


224 


PHYSIOLOGY 


CHAP. 


as    the    effect   of    the   systolic   outflow   of  the   blood   into    the 
arteries. 

Carlile  (1833)  and  Ludwig  (1848),  in  order  to  explain  the 
cardiac  pulse,  took  into  special  consideration  the  conical  form 
assumed  by  the  ventricular  mass  in  systole,  and  the  forward 


Fio.  79. — Oscillations  of  pressure  in  right  ventricle  (V.  D.)  of  horse,  transmitted  through  cardiac 
sound  to  recording  tympanum.  (Marey.)  The  times  at  which  the  first  and  second  heart-sounds 
begin  to  be  heard  are  simultaneously  recorded  by  an  electric  signal. 

inclination  observed  in  the  base  of  the  ventricle,  which  causes  the 
apex  of  the  heart  to  impinge  on  the  wall  of  the  thorax.  But 
since  this  change  of  form  and  movement  of  the  heart  is  the  effect 
of  systolic  evacuation,  it  is  obvious  that  it  cannot  be  adduced  to 
explain  the  sudden  rise  seen  in  the  cardiograms  during  the  period 
of  tension,  i.e.  before  the  blood  begins  to  stream  out  of  the 
ventricles. 

In  a  recent  work  Keith  (1904)  has  taken  up  the  idea  of  Ludwig, 
developing  it  by  subtle  anatomical  arguments  and  with  ingenious 
experimental  methods  for  which  we  refer  the  reader  to  the 
original  memoir.  Keith  maintains  that  the  base  of  the  ventricle 


FIG.  80. — Cardiogram  transmitted  to  cardiograph  from  fifth  left  intercostal  space  in  man.  (Edgren.) 
The  times  at  which  the  first  and  second  heart-sounds  begin  to  be  heard  are  simultaneously 
recorded  by  an  electric  signal. 

rises  slightly  during  presystole.  This  displacement  depends  more 
particularly  on  the  peculiar  disposition  of  the  pectinate  muscles. 
In  consequence  of  this  rise  of  the  base  of  the  ventricle,  it  almost 
meets  the  blood  which  is  driven  towards  it.  When,  on  the 
contrary,  systole  sets  in,  upon  which  the  ventricle  is  restrained  in 
every  dimension,  its  base  is  pushed  out  in  the  opposite  direction. 


VII 


MECHANICS  OF  THE  HEART 


225 


It  follows  that  the  apex  of  the  heart  does  not  approach  the  base, 
but  on  the  contrary  the  base  approaches  the  apex,  so  that  the 
latter  is  energetically  thrust  against  the  thoracic  wall  and  produces 
the  cardiac  beat.  It  may,  however,  be  objected  to  this  ingenious 
experiment  that  the  sharp  lift  produced  by  the  cardiac  impulse 
takes  place  not  during  the  period  of  efflux,  but  in  that  of 
tension. 

The  same  reason  invalidates  the  doctrine  of  the  recoil  (recul 
balastique)  supported  particularly  by  Skoda  (1842)  and  Htffelsheim 
(1854),  which  in  so  far  as  it  assumes  locomotion  of  the  heart 
resembles  the  preceding.  It  is  also  contrary  to  the  fact  that  the 
cardiac  pulse  is  not  confined  to  the  region  of  the  apex  in  the  fifth 
intercostal  space,  but  (as  we  have  seen)  is  even  more  frequently 
accentuated  in  the  fourth  intercostal  space. 


FIG.  81.— The  upper  tracing  is  an  artificial  cardiogram,  obtained  from  a  perfected  model.  The 
lower  tracing  is  a  cardiogram  taken  on  man.  In  both  tracings  the  rise  O  represents  the  effect 
of  presystole  ;  the  rise  V,  the  effect  of  systole.  (Marey.) 

Still  more  inadequate  is  the  theory  maintained  by  Senac 
(1749),  Bahr  (1862)  and  others,  which  derives  the  cardiac  pulse 
from  the  downward  impulse  of  the  apex  in  consequence  of  the 
distension  of  the  arterial  arches  (aortic  and  pulmonary)  determined 
by  the  pressure  produced  in  these  by  each  wave  of  blood  that 
surges  from  the  heart.  We  have  seen  that  the  apex  is  the  least 
mobile  point  of  the  heart  in  the  longitudinal  direction,  because  the 
elongation  of  the  arterial  arches  almost  exactly  compensates  for 
the  systolic  shortening. 

All  these  mechanical  factors  intervene  as  accessory  and  com- 
plementary data  in  the  production  of  the  ictus,  during  the  period 
of  systolic  evacuation ;  but  the  essential  and  fundamental  cause  of 
the  phenomenon  is  the  tension  and  hardening  of  the  heart  during 
the  whole  period  of  systole.  The  heart  is  in  perpetual  contact  with 
the  internal  wall  of  the  thorax  and  the  external  parts  of  the  lungs, 

VOL.  I  Q 


226  PHYSIOLOGY  CHAP. 

which  cover  it  to  a  great  extent ;  but  during  the  period  of  passive 
diastole  or  repose,  its  walls  are  soft  and  easily  compressible,  while 
in  the  systolic  period  they  become  hard  and  tense,  and  this  is', 
enough  to  determine  the  phenomenon  of  ictus.  This  theory, 
adumbrated  by  Harvey,  was  clearly  set  forth  by  Kiwisch  (1846), 
and  upheld  more  recently  by  Baniberger,  and  by  Chauveau  and 
Faivre  (1856) ;  but  Marey  (1863-76)  was  the  first  to  give  convincing 
proof  of  its  accuracy  by  his  ingenious  schemata  of  the  movements 
of  the  heart.  He  succeeded  with  these  in  producing  artificial 
cardiograms,  which  exhibit  all  the  most  important  features  of  the 
cardiograms  obtained  on  man,  as  shown  in  the  two  tracings  of 
Fig.  81. 

The  analytical  study  of  these  features  is  of  great  scientific  and 
practical  interest,  but  we  must  consider  them  together  with  the 
waves  exhibited  by  the  arterial  pulse  and  the  sphygmograms,  with 
which  they  are  intimately  connected  by  their  origin. 

X.  The  systolic  movements  of  the  heart  in  the  period  of  tension 
must,  since  they  determine  a  sudden  elevation  of  the  intercostal 
spaces  of  the  precordial  region,  produce  a  rhythmical  dilatation  of 
the  thoracic  cavity,  in  proportion  with  the  energy  and  rapidity  of 
the  impact.  Further,  the  diminution  of  the  total  volume  of  the 
heart  during  the  period  of  systolic  efflux  until  it  reaches  meiocardia 
is  commensurate  with  the  quantity  of  blood  expelled  from  the 
arteries.  Half  this  blood,  passing  through  the  pulmonary  system, 
does  not  leave  the  thoracic  cavity ;  but  the  other  half,  passing 
through  the  aortic  system,  issues  rapidly  from  the  thorax,  pro- 
ducing a  comparative  vacuum,  which  cannot  be  compensated  by 
the  blood  that  simultaneously  enters  the  thorax  by  the  venae 
cavae.  During  systole,  therefore,  the  thoracic  cavity  must,  in 
virtue  of  distinct  mechanical  conditions  which  succeed  each  other, 
develop  an  aspiration,  capable  of  being  felt  in  the  intercostal 
spaces  not  in  contact  with  the  heart — in  the  lungs,  the  diaphragm 
and  the  veins  adjacent  to  the  thorax. 

In  thin  persons  it  is,  in  fact,  easy  to  see  coincidently  with 
systole,  a  depression  of  the  intercostal  spaces,  to  which  the  name  of 
negative  cardiac  pulse  has  been  given  (to  distinguish  it  from  the 
positive  pulse  that  can  be  observed  in  the  region  of  the  apex  of 
the  heart  and  its  vicinity).  At  the  same  moment  there  is  also  a 
negative  pulmonary  pulse,  i.e.  a  gentle  inspiratory  movement  of 
the  lungs  which,  when  the  glottis  is  open,  may  produce  a  systolic 
diminution  in  the  pressure  of  the  air  contained  in  the  buccal  cavity 
or  nasal  fossae.  It  is  also  possible  to  detect  a  negative  pulse  of 
the  abdominal  wall  in  the  epigastric  region,  which  is  the  effect  of 
an  aspiration  exerted  by  the  thoracic  cavity  on  the  diaphragm. 
Lastly,  it  is  possible  also  to  observe  a  negative  systolic  pulse  in  the 
jugular  veins  due  to  the  same  cause,  although  here  it  is  probable 
that  other  mechanical  factors  co-operate,  which  are  independent  of 


VII 


MECHANICS  OF  THE  HEAET 


227 


the  changes  of  intrathoracic  pressure,  and  depend  on  variations 
of  pressure  within  the  right  auricle. 

Many  physiologists  have  exercised  their  critical  and  technical 
abilities  upon  these  phenomena  of  negative  pulsation,  the  indirect 
effects  of  the  positive  cardiac  pulse  and  of  nieiocardia.  Buisson 
(1861)  was  the  first  to  describe  the  negative  thoracic  pulse,  and 
the  negative  pulmonary  pulse ;  Voit  (1805)  again  observed  the 


Co 


FIG.  82. — Ara,  Pneumograiu  taken  from  the  nostrils  ;  C'a,  sphygmogram  from  the  cuiotids,  recorded 
simultaneously  with  open  glottis.  (Mosso.)  ;. It  will  be  seen  thatlthe  inspiratory  movement 
precedes  the  carotid  pulse. 

rhythmical  systolic  inspirations,  and  held  them  to  be  the  effect  of 
the  diminution  in  the  heart's  volume  ;  Ceradini  (1869)  clearly 
perceived  the  mechanical  consequences  of  nieiocardia  and  auxo- 
cardia,  but  made  no  experimental  study  of  them  ;  Paul  Bert 
(1870),  among  the  oscillations  of  air-pressure  within  the  trachea  of 
a  dog,  included  those  dependent  on  cardiac  movements ;  Loven 
(1870)  took  tracings  of  the  negative  thoracic,  and  the  positive  pulse 
of  the  radial  artery,  and  observed  them  to  be  simultaneous  ;  Landois 
(1876)  obtained  tracings  of  the  cardiac  oscillations  of  air-pressure 
of  the  nasal  cavities  (which  he  termed  cardio-pneumatic  curves), 


FIG.  83. — Co,  Cardiogram  taken  on  man  at  fifth  intercostal  space  ;  Na,  pneumogram  taken  from 
nostrils.     Simultaneously  recorded  with  open  glottis.    (Mosso.) 

and  was  the  first  to  distinguish  the  negative  pulse  which  can  be 
verified  at  each  systole  when  the  glottis  is  open,  from  the  positive 
pulse  which  occurs  when  the  glottis  is  closed,  and  the  nasal 
cavities  function  as  a  space  distinct  from  those  of  the  pulmonary 
passages,  in  which  there  is  diminished  pressure  with  each  wave  of 
blood  that  inundates  the  arterial  vessels. 

Mosso  (1878)  was,  however,  the  first  who  grasped  this  subject 
fully,  and  employed  an  exact  experimental  technique.  In  his  cardio- 
pneumatic  curves  obtained  with  an  ordinary  Marey's  tambour 


228 


PHYSIOLOGY 


CHAP 


connected  with  the  nasal  cavities,  he  was  able  to  distinguish  a  first 
inspiratory  depression,  due  to  the  systolic  lift  of  the  intercostal 
spaces  of  the  precordial  region,  from  a  second,  later  depression  due 
to  meiocardia.  This  is  plain  in  the  two  tracings  (Figs.  82  and  83), 
in  the  first  of  which  the  negative  pneumograin  of  the  nasal  fossae 
is  recorded  simultaneously  with  the  sphygmogram  of  the  carotid, 


FIG.  84. — jV«,  Positive  pneumogram  taken  from  nostrils  with  •efteft- glottis ;  Co,  carotid 
sphygmogram,  recorded  simultaneously.     (Mosso.) 

and  in  the  second  with  the  thoracic  cardiogram.  Repeating  the 
experiment  with  closed  glottis,  the  negative  pneumogram  is  trans- 
formed into  the  positive  (as  shown  on  Fig.  84).  All  who,  like  the 
author,  are  incapable  of  holding  their  breath  without  closing  the 
glottis,  obtain,  on  the  repetition  of  Mosso's  experiment,  positive 
pneumograms  only.  This  was  the  case  (as  Mosso  points  out)  with 
Terne  van  der  Heul  (1867),  who,  on  making  these  experiments 
under  the  guidance  of  Bonders,  invariably  obtained  results  that 
contradicted  the  above  theory. 

If  a  sound  is  introduced  into  the  oesophagus,  covered  at  the 


FIG.  85.— I,  Cardiac  sphygmogram  from  dog,  transmitted  from  oesophageal  iexplorer  to  recording 
tambour  during  long  expiratory  pause;  II,  effects  of  cardiac  beats  transmitted  from  rectal 
explorer,  recorded  simultaneously.  (Luciani.) 

end  by  a  very  fine  rubber  membrane  like  the  finger  of  a  glove, 
the  canal  is  transformed  into  an  intrathoracic  cavity  communi- 
cating with  the  exterior  in  such  a  way  that  (on  connecting  up 
the  external  opening  of  the  sound  with  a  tambour  and 
writing  lever)  the  vibrations  produced  within  the  thorax  can 
all  be  traced  on  the  rotating  cylinder.  The  negative  oscilla- 
tions are  recorded  by  descending,  the  positive  by  ascending 
lines.  We  were  the  first,  in  1877,  to  introduce  this  method  into 


VII 


MECHANICS  OF  THE  HEART 


229 


physiological  technique,  and  to  recognise  in  the  tracings,  not 
merely  the  large  oscillations  dependent  on  the  respiratory  move- 
ments, but  also  the  lesser  variations  due  to  the  movements  of 
the  heart. 

We  found   the  cardiac  sphygmogranis  obtained  by  the  oeso- 
phageal  method  to  be   of   very  complex  form,   varying   greatly, 


FIG.  86. — From  same  dog  as  preceding  figure,  after  section  of  cervical  cord  between  fifth  and  .sixth 
vertebrae.  (Luciani.)  It  will  be  seen  that  diaphragmatic  respiration  alone  persists.  I,  In- 
spirations ;  E,  expirations.  The  cardiac  sphygmogranis  are  reduced  to  minute  oscillations, 
and  are  only  visible  on  the  oesophageal  tracing. 

particularly  in  their  dimensions,  with  the  condition  of  the 
animal  (Figs.  85  and  86).  We  also  found  that  they  could  not  be 
dependent  exclusively  on  the  effects  of  meiocardia  and  auxocardia, 
but  were  influenced  also  by  the  nature  of  the  relations  of  contact 
between  the  heart  and  the  oesophagus,  since  on  opening  the 
thoracic  cavity  they  do  not  entirely  disappear,  but  are  considerably 
modified  (Fig.  87). 

Leon  Fredericq  (1888)  took  up  this  point  again  in  order  to 
make  a  more  detailed  analysis  of  the  oesophageal  sphygmogranis, 
and  obtained  complex  forms  of  oscillations  which  closely  resembled 
the  very  interesting  oscillations  which  he  observed  in  the  cavity  of 


FIG.  87.— Cardiac  sphygmograms  transmitted  from  oesophageal  explorer  during  apnoea  of  forced 
artificial  respiration  in  anaesthetised  dog.  (Luciani.)  C,  With  closed  thorax  ;  A,  with  opened 
thorax  ;  C',  A',  the  same  on  another  anaesthetised  dog  ;  C",  A",  the  same  on  a  third  cnrarised 
dog. 

the  auricles  (see  Fig.  68,  p.  207).  From  this  he  concluded  that 
they  were  dependent  on  a  direct  transmission  to  the  oesophagus  of 
the  active  and  passive  movements  of  the  left  auricle,  pointing  out 
the  intricate  anatomical  relations  between  these  two  organs.  He 
denied  that  they  were  in  any  way  dependent  on  the  effects  of 
meiocardia  or  auxocardia,  because  they  are  not  abolished  by  the 
opening  of  the  thorax.  This  last  conclusion,  however,  does  not 
take  into  account  the  fact,  which  we  discovered  twelve  years 


230  PHYSIOLOGY  CHAP. 

earlier,  that  the  pulsations  in  the  oesophagus  are  considerably 
changed  and  simplified  after  opening  of  the  thorax. 

Martius  (1888),  on  the  other  hand,  while  almost  contemporary 
with  Fredericq,  considered  only  the  effects  of  meiocardia  and  auxo- 
cardia  in  interpreting  the  oesophageal  pulsations,  and  thus  came 
to  a  one-sided  conclusion  in  the  opposite  direction. 

XL  Before  leaving  this  interesting  subject  of  cardiac 
mechanism,  it  is  necessary  to  form  some  approximate  conception  of 
the  work  that  is  usually  performed  by  the  heart  in  a  unit  of  time. 

The  work  of  the  heart  is  equal  in  the  time  unit  to  the  weight 
of  the  blood  it  is  capable  of  moving,  multiplied  by  the  height  of 
the  pressure  to  which  the  said  weight  is  lifted.  To  determine  this 
work  it  is  necessary  to  form  a  proper  appreciation  on  the  one 
hand  of  the  mechanical  value  of  each  cardiac  revolution,  i.e.  of  the 
quantity  of  blood  that  passes  from  veins  to  arteries  in  the  said 
unit  of  time ;  on  the  other,  of  the  height  of  pressure  in  the  arteries 
nearest  to  the  heart. 

The  weight  of  blood  driven  into  the  arteries  at  each  systole 
depends  both  on  the  degree  of  diastolic  filling  (auxocardia),  and  on 
the  degree  of  systolic  evacuation  (meiocardia).  It  is  very  difficult 
to  arrive  at  an  exact  determination  of  this  weight,  since  it  varies 
with  varying  conditions.  The  values  of  185*5  and  of  180  grins, 
cited  by  Volkmann  and  Yierordt  in  calculating  the  work  of  the 
heart  are  certainly  exaggerated.  The  values  adopted  by  Fick 
(50-75  grms.),  by  Tigerstedt  (50  grins.),  and  by  Zuntz  (60  grms.) 
are  probably  nearest  to  the  truth. 

On  the  other  hand,  the  mean  pressure  of  the  aorta  may  be  taken 
as  approximately  equal  to  150  mm.  Hg,  i.e.  in  round  figures  to  a 
column  of  blood  2  metres  high,  and  the  pressure  in  the  pulmonary 
artery  may  be  taken  as  about  a  third  of  the  aortic  pressure. 

Assuming  that  the  left  ventricle  drives  some  60  grms.  of  blood 
into  the  aorta  at  each  systole  under  a  pressure  of  2  in.  of  blood,  and, 
allowing  for  the  velocity  acquired  by  the  same,  which  is  a  negligible 
quantity,  we  obtain  a  yield  of  120  grammetres  at  every  revolution. 
,  Given  72  revolutions  per  minute,  it  is  easy  to  calculate  that  the 
work  done  by  the  left  ventricle  in  24  hours  represents  about 
12,450  kilograrnmetres.  If  a  third  of  this,  -i.e.  4150  kilogram- 
metres,  be  added  as  the  approximate  work  of  the  right  ventricle, 
the  total  work  of  the  heart  in  24  hours  may  be  reckoned  as 
16,600  kilograrnmetres. 

The  friction  to  which  the  blood  is  submitted  in  its  passage 
through  the  closed  vascular  system  transforms  the  entire  work  of 
the  heart  into  heat.  Starting  from  the  fact  that  425  kilogram- 
metres  are  necessary  for  the  development  of  1  calorie,  the  16,600 
kilogrammetres  of  the  heart's  daily  work  represent  some  39  calories, 
corresponding  with  the  heat  developed  by  the  combustion  of  less 
than  5  grms.  of  carbon. 


vii  MECHANICS  OF  THE  HEART  231 

BIBLIOGRAPHY 

O.  KURSCHNER.     Herzthtitigkeit.    Wagner's  Handwbrterbuch  der  Physiol.,  Zweiter 

Band,  S.  30-107.     Braunschweig,  1844. 
O.   LUDWIG.     Lehrbuch  der  Physiologie  des  Menschen.    Zweite  Auflage,   Zweiter 

Band.     Leipzig  und  Heidelberg,  1861. 

R.  TIGERSTEDT.     Lehrbuch  der  Physiologie  des  Kreislaufes.     Leipzig,  1863. 
CHAUVEAU  e  ARLOING.    Coeur  (Pliysiologie),  Dictionnaire  encycloped.  des  sciences 

medicales,  tome  xviii.  pp.  314-382.     Paris,  1876. 
MAREY.    La  Circulation  du  sang  a  1'etat  physiologique  et  dans  les  maladies.    Paris, 

1881. 
L.  LUCIANI.    Deir  attivita  della  diastole  cardiaca.    Rivista  clinica.    Bologna,  1871, 

1874,  1876. 
A.  STEFANI.    Cardiovolume,  pressione  pericardicae  attivita  della  diastole.    Memoria 

letta  all'  Accademia  medico -chirurgica  di  Ferrara  il  5  agosto  1891. 
O.  CERADINI.    II  Meccanismo  delle  valvole  semilunari  del  cuore.    Gazzetta  medica 

italiana-lombarda.     Milano,  1871. 
O.  PALADINO.    Contribuzione  all'  anatomia,  istologia  e  iisiologia  del  cuore.     Movi- 

mento  medico-shirurgico.    Napoli,  1876. 
L.  LUCIANI.     Delle  oscillazioni   della   pressione   intratoracica   e    intraddominale. 

Archivio  di  Bizzozero,  anno  II.     Torino,  1877. 

A.  Mosso.     Sul  polso  negativo.    Archivio  di  Bizzozero,  anno  II.     Torino,  1878. 
L.   FREDERICQ.     La  Pulsation  du  coeur  chez  le  chien.     Travaux  du   laboratoire, 

tome  ii.  1887-88. — Arch,  internationales  de  physiol.,  vol.  v.  1907. 
J.   G.  EDGREN.     Cardiographische  und   sphygmographische  Studien.     Skandina- 

visches  Archiv  fur  Physiologie,  Erster  Band,  S.  66-151.     Leipzig,  1889. 
L.  KREHL.     Beitrage  zur  Kenntnis  der  Fiillung  und  Entleerung  des  Herzens.  Aus 

dem  physiologischen  Institut  zu  Leipzig,     xvii.  Band  der  Abhandhmgen  der 

K.  Sachs.  Gesell.  d.  Wissenschaften.     Leipzig,  1891. 
TK;ERSTEDT.     Intrakardialer  Druck  und  Herzstoss.     Ergebnisse  der  Physiologie, 

1902.     (60  works  are  cited  in  this  article.) 
E.    EBSTEIX.     Die  Diastole  des  Herzens.  Ergebnisse  der  Physiologie,   1906.      (187 

works  are  cited  in  this  article. ) 

Recent  English  Literature. 
AV.  P.  LOMBARD  and  W.  B.  PILLSBUIIY.   Secondary  Rhythms  of  the  Normal  Human 


Heart.     Amer.  Journ.  of  Physiol.,  1900,  iii.  201. 
R.   CUSHNY.     On  Periodic  Variatic 


A.  R.   CUSHNY.     On  Periodic  Variations  in  the  Contractions  of  the  Mammalian 

Heart.     Journ.  of  Physiol.,  1899-1900,  xxv.    49*. 
J.  A.  MACWILLIAM.     Rigor  Mortis  in  the  Heart  and  the  State  of  the  Cardiac  Cavities 

after  Death.     Journ.  of  Physiol.,  1901-2,  xxvii.  336. 
D.   J.   LINGLE.     Restorers  of  the  Cardiac  Rhythm.       Amer.  Journ.   of  Physiol., 

1905,  xiv.  433. 
Y.  HENDERSON.    The  Volume  Curve  of  the  Ventricles  of  the  Mammalian  Heart,  and 

the  Significance  of  this  Curve  in  Respect  to  the  Mechanics  of  the  Heart-Beat 

and  the  filling  of  the  Ventricles.      Amer.  Journ.  of  Physiol.,  1906,  xvi.  325. 
T.  LEWIS  and  A.  S.  MACNALTY.    A  Note  on  the  Simultaneous  Occurrence  of  Sinus 

and  Ventricular  Rhythm  in  Man.     Journ.  of  Physiol.,  1908,  xxxvii.  445. 


CHAPTEK   VIII 

THE   BLOOD-STKEAM  :    MOVEMENT    IN   THE    VESSELS 

SUMMARY. — 1.  .Fundamental  laws  of  hydrodynamics  for  passage  of  fluid  through 
rigid  tubes.  2.  Application  of  these  laws  to  haemodynaiuics.  3.  Mechanical 
effects  of  elasticity  of  vessel  walls  and  intermittence  of  flow  of  blood  from  heart ; 
laws  of  wave  motion.  4.  Method  of  measuring  and  automatically  registering 
variations  in  blood  pressure.  5.  Principal  results  obtained.  6.  Methods  of  measur- 
ing velocity  of  circulation  ;  experimental  results.  7.  Sphygmography  and  sphygmo- 
grams  representing  pulsatory  oscillations  in  pressure.  8.  Comparison  of  cardiograms 
and  sphygmograms  registered  simultaneously,  indicating  duration  of  principal 
phases  of  cardiac  cycle  in  man.  9,  Comparison  of  several  sphygmograms  registered 
simultaneously  from  arteries  at  different  distances  from  the  heart,  indicating  rate 
of  transmission  of  primary  and  of  dicrotic  wave.  10.  Tachymetry  and  tachygrams 
representing  pulsatory  variations  in  current  velocity.  II.  Plethysmography  and 
plethysmograms  representing  pulsatory  oscillations  in  the  volume  of  the  arteries. 
12.  Schema  of  mechanical  conditions  of  the  circulation  in  the  three  great  vascular 
systems  ;  determination  of  duration  of  the  entire  circulation.  Bibliography. 

WHEN  the  circulation  is  observed  under  the  microscope  (see  Chap. 
VI.,  8)  it  is  easy  to  detect  a  phenomenon  which  is  among  the 
most  fundamental  in  Haemodynamics :  the  movement  of  blood  in 
the  vessels  is  continuous  ;  continuous  and  rhythmically  accelerated 
in  the  arteries,  continuous  and  constant  in  the  veins.  The  analysis 
of  this  complex  phenomenon  in  its  details  and  in  its  elements,  the 
determination  of  the  mechanical  conditions  on  which  it  depends, 
and  the  laws  by  which  it  is  governed,  form  the  contents  of  this 
chapter. 

I.  The  movement  of  the  blood  from  the  heart  through  the 
vessels  is  regulated  and  determined,  like  the  movement  of  water 
driven  rhythmically  through  a  tube  from  a  pump,  by  two 
antagonistic  influences :  the  energy  developed  from  the  heart,  or 
pump,  which  drives  the  fluid  through  the  vessels;  and  the 
resistance  represented  by  the  internal  walls  of  the  vessels,  owing 
to  the  adhesion  of  the  fluid,  and  its  viscosity.  The  velocity  of  each 
molecule  of  fluid  is  proportional  to  the  difference  between  the 
impulses  felt  by  each  a  tergo  and  a  f route.  The  more  the  driving 
force  overcomes  the  sum  of  the  resistances,  the  faster  will  be  the 
flow  of  a  fluid  through  the  system.  In  order,  however,  to 
form  a  more  exact  and  concrete  idea  of  the  mechanism  of  the 
movement  of  fluids,  it  will  be  well  to  review  certain  principles 

232 


CH.  viii  BLOOD-STEEAM  :   MOVEMENT  IN  VESSELS    233 

of  hydrodynamics,  which  are  intimately  connected  with  haemo- 
dynamics. 

(a)  Let  us  take  the  simplest  case  of  a  fluid  contained  in  a  vessel 
having  an  outlet  in  its  base.  As  soon  as  this  is  opened,  the 
resistance  offered  to  the  hydrostatic  pressure  over  the  outlet 
vanishes,  and  the  fluid  pours  out  through  the  opening.  Accord- 
ing to  Torricelli's  theorem  (1643),  the  velocity  (v)  with  which  a  fluid 
escapes  is  (apart  from  the  resistance  it  encounters)  exactly  equal 
to  that  which  a  body  would  acquire  in  falling  free  through  the 
height  of  the  column  of  fluid  to  the  orifice.  It  is  therefore  in- 
dependent of  the  nature  of  the  fluid,  and  depends  on  the  pressure, 
i.e.  on  the  height  (H)  of  the  column  of  fluid,  and  is  proportional 
to  the  square  root  of  this  height,  i.e.  it  increases  as  1,  2,  or  3,  when 
the  increment  of  height  is  as  1,  4,  9.  If  the  acceleration  due  to 
gravity  at  each  second  (which  =  9'8  in.)  is  represented  as  g,  we 
have  :  — 


(5)  When  a  rigid  horizontal  tube  is  joined  to  the  orifice  of  the 
same  vessel  (in  which  a  column  of  fluid  is  maintained  at  equal 
height  and  constant  diameter  throughout  its  length)  the  velocity 
of  outflow,  and  therefore  the  amount  of  fluid  escaping  from  the 
end  of  that  tube,  will  be  less  than  in  the  previous  case,  because  a 
portion  of  the  available  hydrostatic  pressure  will  be  applied  to 
overcoming  the  new  resistance  which  the  fluid  encounters  in  its 
passage  through  the  tube,  and  cannot  therefore  add  to  the  velocity 
of  the  escaping  fluid. 

The  resistances  are  represented  by  the  internal  friction  between 
the  molecules  of  fluid,  which  are  forced,  partly  by  the  adhesion  of 
the  external  layer  of  fluid  to  the  walls  of  the  tube,  partly  by 
viscosity  (see  p.  151),  to  glide  one  over  the  other.  As  we  have  seen 
elsewhere  (p.  189)  the  velocity  of  the  single-current  threads,  into 
which  we  may  consider  the  cylinder  of  fluid  driven  through  the 
tube  to  be  broken  up,  increases  from  the  periphery  to  the  axis  of 
the  cylinder,  where  it  is  maximal.  The  mean  velocity  corresponds 
with  half  the  maximal  velocity  observed  in  the  axis. 

Since  liquids  are  incompressible,  i.e.  can  neither  be  compressed 
nor  the  reverse  in  their  passage  through  tubes,  it  follows  that 
their  average  velocity  must  be  equal  at  every  section  of  the  same, 
also  that  the  amount  passing  every  section  in  the  unit  of  time 
must  be  equal. 

Owing  to  internal  friction  the  fluid  exerts  a  lateral  pressure  on 
the  walls  of  the  tube,  which  can  be  measured  by  fixing  manometer 
tubes,  or  piezometers,  perpendicular  to  the  axis  (Fig.  88).  The 
height  to  which  the  fluid  ascends  in  the  piezometers  decreases 
regularly  from  that  in  the  tube  nearest  the  orifice  by  which  it 
enters  to  that  nearest  the  outflow,  so  that  the  highest  points  of 


234 


PHYSIOLOGY 


OHAV. 


the  columns  of  fluid  in  all  the  piezometers  can  be  joined  by  a 
straight  line.  This  straight  line,  which  represents  the  gradual 
fall  of  lateral  pressure  along  the  tube,  is  more  or  less  steep  in 
proportion  to  the  velocity  of  outflow. 

As  shown  in  the  diagram,  the  total  force  represented  by  the 
height  H  of  the  column  of  fluid  contained  in  the  vessel  falls  into 
two  parts :  that  employed  in  overcoming  the  resistance  offered  to 
the  free  passage  of  the  fluid  through  the  tube  /«-',  and  that  employed 
in  driving  the  fluid  through  the  tube  h.  The  first  is  termed  lateral 
pressure  or  resistance-head,  the  second  velocity-head. 

(c)  When  the  tube  connected  with  the  vessel  varies  in  diameter 


FIG.  8S. — Schema  to  demonstrate  the  laws  which  regulate  the  flow  of  a  liquid,  at  constant  pressure, 
through  a  conducting  tube  with  rigid  walls  and  uniform  diameter. 

in  its  different  parts,  the  same  fundamental  law  applies  as  has  been 
laid  down  for  tubes  of  constant  bore.  Since  fluid  is  incompres- 
sible, an  equal  amount  must  flow  through  every  section  of  the  tube, 
independent  of  its  diameter  in  the  time-unit. 

In  consequence  of  this  law,  the  velocity  of  the  current  in 
sections  of  tubes  that  vary  in  diameter  stands  in  inverse  pro- 
portion to  the  sectional  area. 

Since  the  resistance  in  the  wider  parts  of  the  tube  is  less  than 
in  the  narrower  sections,  it  follows  that  the  fluid  requires  less  force 
to  propel  it  through  the  former  than  it  does  to  pass  through  the 
latter.  The  lateral  pressure  accordingly  sinks  more  slowly  in  the 
former  and  more  rapidly  in  the  latter,  as  shown  in  Fig.  89.  At 
points  where  a  wider  section  of  the  tube  passes  into  a  narrower, 
velocity  rises,  and  there  is  considerable  diminution  of  pressure, 
owing  to  the  greater  resistance  which  the  fluid  encounters ;  where, 
on  the  contrary,  a  wider  section  follows  a  narrower,  velocity  falls, 
while  pressure  on  the  contrary  increases  or  remains  unchanged,  or 


vin       BLOOD-STKEAM :   MOVEMENT  IN  VESSELS       235 

falls.  This  paradoxical  fact  was  explained  by  Donders  as  the 
result  of  the  formation  of  vortices,  at  the  base  of  the  dilatation 
already  referred  to  (Chap.  VII.  p.  190).  It  is  certain  that  the 
vortices  consume  a  certain  amount  of  force.  When  this  con- 
sumption is  considerable,  pressure  falls ;  when,  on  the  other  hand, 
it  is  inconsiderable,  pressure  either  remains  unaltered,  or  increases, 
as  must  always  occur  in  consequence  of  the  diminution  of  velocity. 
It  is  obvious  that  where  the  dilatations  and  constrictions  of  the 
tube  occur  gradually  instead  of  suddenly,  the  alterations  of  velocity 
and  pressure  in  its  different  sections  must  obey  the  same  laws,  with 
the  simple  difference  that  they  are  produced  slowly,  so  that  their 


Fi<:.  89. — Schema  similar  to  that  of  preceding  figure.     The  rigid  conducting  tube  of  equal  diameter 
is  here  replaced  by  a  tube  of  unequal  diameter  in  its  various  parts.     (Rollett.) 

course  is  represented  by  a  curved  rather  than  by  a  straight  gradient, 
as  in  the  preceding  case. 

(d)  When  the  tube  connected  with  the  vessel  branches  into  two 
or  more  smaller  tubes  so  that  the  bed  of  the  current  is  widened, 
i.e.   the  sum  of  the  sectional  area  of  the   branches  presents   a 
larger  diameter  than  the  original  tube,  the  result  is  complicated. 
Since  the  sectional  area  of  the  current  is  enlarged,  the  sum  of  the 
resistances  should  be  diminished ;  on  the  other  hand,  the  branching 
of  the  tube  must  introduce  new  resistances,  which  increase  with 
the  size  of  the  angle  made  by  the  branches.     These  two  opposite 
conditions  are    to   a   certain   extent   compensatory.      Jacobson's 
experiments  (1860),  however,  show  that  the  preponderating  in- 
fluence is  always  the  widening  of  the  bed,  by  which  the  amount  of 
fluid  passing  through   each   cross-section  of  the  system   in   the 
time-unit  is  increased. 

(e)  If  the  tube  after  branching  so  as  to  widen  the  bed  of  the 


236  PHYSIOLOGY  CHAP. 

current,  unites  again  into  a  single  outflow  tube  in  which  the 
sectional  area  is  once  more  reduced,  we  obtain  a  system  of  canals 
which  schematically  represents  the  circulatory  system.  Under 
these  complex  conditions  the  same  fundamental  laws  hold  good 
that  we  have  been  discussing  for  the  preceding  simple  cases. 

The  rate  of  flow  to  the  different  parts  of  the  system  is  inversely 
proportional  to  the  sum  of  the  cross-sections,  i.e.  to  the  width  of 
the  current  bed.  Since  the  same  amount  of  fluid  enters  the 
system  by  the  inflow  tube,  and  leaves  the  system  by  the  outflow 
tube,  in  the  time-unit,  so  the  same  amount  of  fluid  must  pass 
through  every  section  of  the  system  in  the  same  time,  with  a 
correspondingly  greater  velocity  where  the  sectional  area  is 
narrower,  with  less  velocity  where  it  is  wider. 

The  pressure  at  every  point  of  the  system  must  be  proportional 
to  the  sum  of  the  resistances  which  the  fluid  has  to  overcome 
before  reaching  the  outflow.  Since  the  section  of  each  tube 
decreases  as  the  system  branches,  while  the  total  sectional  area 
increases,  so  the  sum  of  the  resistances  must  increase  with  the 
former  and  decrease  with  the  latter.  Which  of  these  two  condi- 
tions has  the  preponderating  influence  ?  Experience  shows  that 
when  the  branching  of  the  system  goes  as  far  as  the  production  of 
capillary  tubes,  the  sum  of  the  resistances  increases  in  these  to 
such  an  extent  that  it  cannot  be  compensated  by  the  widening, 
however  great,  of  the  bed  of  the  stream.  In  a  system  of  capillary 
vessels  the  velocity  of  outflow  is,  according  to  Foiseuille,  propor- 
tional, not,  as  in  tubes  of  larger  diameter,  to  the  square,  but  to  the 
fourth  power  of  the  radius. 

II.  All  these  laws,  in  so  far  as  they  concern  pressure,  velocity, 
and  outflow,  are  perfectly  applicable  to  the  vascular  blood  system, 
since  this  consists  of  canals  which  ramify  until  they  are  reduced 
into  a  capillary  network  with  a  vast  extension  of  the  bed  of  the 
current,  and  then  gradually  form  into  canals  again,  each  of  which 
has  individually  a  wider  cross-section,  but  which  as  a  whole  make 
up  a  narrower  channel.  Setting  aside  for  the  moment  the  differ- 
ences between  the  circulatory  system  and  the  system  of  conducting 
tubes  which  we  have  just  been  considering,  it  is  possible  to  formu- 
late three  general  laws  which  are  at  the  base  of  the  circulatory 
phenomena. 

(a)  Laws  of  Current. — Under  normal  circulatory  conditions, 
the  amount  of  blood  that  flows  out  of  the  heart  through  the  arteries 
in  the  time-unit  is  exactly  equal  to  that  which  flows  into  the 
heart  by  the  veins ;  the  amount  of  blood  which  enters  or  leaves 
the  right  or  left  heart  is  exactly  equal  to  that  which  leaves  or 
enters  the  left  or  right  heart ;  in  more  general  terms,  the  amount 
of  blood  which  passes  through  any  total  cross-section  of  the  circu- 
latory system  is  exactly  equal  to  that  which  passes  in  the  same 
time  through  any  other  total  cross-section  of  the  same  system. 


vin       BLOOD-STKEAM :   MOVEMENT  IN  VESSELS       237 

The  validity  of  this  law  would  be  absolute  if  the  blood,  which — like 
all  fluids — is  incompressible,  were  circulating  in  a  system  of  rigid 
tubes.  But  since  the  walls  of  the  vessels  are  extensible  and  elastic, 
it  is  evident  that  there  may  be  a  temporary  infraction  of  it  without 
disturbing  the  fundamental  conditions  of  the  circulation.  The 
mass  of  blood  driven  through  the  pulmonary  arteries,  e.g.,  may  for  a 
few  seconds  be  greater  than  that  which  simultaneously  enters  the 
left  auricle  through  the  four  pulmonary  veins :  this  must  produce 
•a  certain  degree  of  pulmonary  congestion,  compatible  with  life. 
If,  however,  this  condition  be  maintained  too  long,  and  if  the 
converse  phenomenon  does  not  immediately  succeed  it,  so  that 
normal  circulatory  conditions  are  restored,  the  congestion  in  the 
pulmonary  vessels  will  obviously  increase  to  such  an  extent  in  a 
short  time  that  it  presents  an  invincible  obstacle  to  the  now  of 
blood.  Obviously,  therefore,  the  above  law  has  only  a  relative 
value,  when  the  time-unit  is  taken  as  an  interval  of  a  few  seconds ; 
it  has  an  absolute  value  where  a  longer  period,  i.e.  of  one  or  more 
minutes,  is  taken. 

(&)  Law  of  Velocity. — It  follows  as  the  necessary  result  of  the 
law  of  outflow  that  the  velocity  is  inversely  proportional  to  the 
cross-section,  in  the  different  parts  of  the  vascular  system.  In 
order  to  determine  the  proportion  in  which  velocity  alters  in  the 
different  parts  of  the  circulatory  system  it  is  enough  to  measure 
the  total  sectional  area  of  the  vessels  in-  that  part.  This  is  only 
possible  with  the  large  arteries  and  veins  nearest  the  heart,  which 
is  the  centre  of  the  system ;  it  is  necessary,  however,  to  measure 
them  not  on  the  dead  body,  but  on  the  living  subject,  under  the 
most  normal  circulatory  conditions  possible,  so  as  to  obtain  the 
sectional  area  under  physiological  tension  and  filling  of  the  vessels. 
Since  the  total  sectional  area  or  current  bed  increases  slowly  on  the 
one  hand,  from  the  large  to  the  small  arteries,  and  rapidly  from 
these  to  the  capillaries  ;  and  on  the  other  hand,  falls  rapidly  from  the 
capillaries  to  the  small  veins,  and  slowly  from  these  to  the  large 
veins,  it  may  be  stated  in  general  terms  that  velocity  alters  in  the 
inverse  sense  and  same  proportion.  Since,  further,  the  sectional 
area  of  the  aorta  is  less  than  the  sum  of  the  sectional  area  of  the 
two  venae  cavae,  while,  on  the  other  hand,  the  sectional  area  of  the 
pulmonary  artery  is  larger  than  the  sum  of  the  sectional  area  of 
the  four  pulmonary  veins,  the  velocity  of  the  blood-stream  in  the 
systemic  circulation  will  be  maximal  in  the  aorta,  minimal  in  the 
aortic  capillaries,  medium  in  the  venae  cavae;  while  in  the 
pulmonary  system  it  will  be  maximal  in  the  pulmonary  veins, 
minimal  in  the  capillaries,  medium- in  the  arteries. 

The  difference  in  mean  velocity  of  the  flow  in  the  vessels  of  the 
pulmonary  and  aortic  circulations  can  also  be  arrived  at  a  priori, 
starting  from  the  fact  that  the  capacity  of  the  first  system  is  to 
that  of  the  second  as  2  : 11.  It  follows  that  the  pulmonary  circula- 


328  PHYSIOLOGY  CHAP. 

tion  is  completed  at  a  mean  velocity  some  five  times  greater  than 
that  of  the  aortic  circulation  (Jolyet,  1880). 

(c)  Law  of  Pressure. — Seeing  that  pressure  in  the  individual 
parts  of  the  system  is  determined  by  the  sum  of  the  resistances 
which  the  blood  has  to  overcome  in  order  to  reach  the  centre  of  the 
circulation,  i.e.  the  heart,  it  follows  that  it  must  diminish  progres- 
sively in  both  the  aortic  and  the  pulmonary  circulations,  from 
arteries  to  capillaries,  and  from  these  to  the  veins,  in  which  last,  as 
we  have  seen,  it  falls  to  zero.  Since  the  sum  of  the  resistances, 
caeteris  paribus,  derives  mainly  from  the  friction  surface,  and  this 
increases  slowly  from  large  to  small  arteries,  rapidly  from  the  latter 
to  the  capillaries,  and  then  diminishes  again  slowly  from  capillaries 
to  veins,  it  follows  that  pressure  must  fall  slowly  in  the  arteries, 
rapidly  in  the  capillaries,  and  then  slowly  again  in  the  veins. 

Broadly  speaking,  it  may  be  assumed  that  the  sum  of  the 
resistances  which  the  blood  expelled  from  the  right  heart  has  to 
overcome  in  order  to  pass  through  the  pulmonary  system,  in  com- 
parison with  that  overcome  by  the  left  heart  in  traversing  the 
systemic  system,  is  approximately  proportional  to  the  difference  in 
capacity  of  the  two  systems,  so  that  the  mean  pressure  in  the 
pulmonary  circulation  must  be  correspondingly  less  than  that  of 
the  aortic.  The  dissimilar  thickness  of  wall  in  the  two  ventricles 
is,  as  we  have  seen,  an  indicator  of  dissimilar  work  or  force  expended 
by  the  two  systems. 

III.  The  circulatory  system  differs  from  the  artificial  system  of 
rigid  tubes  in  two  important  particulars — the  complete  elasticity 
of  its  walls  and  the  intermittent  character  of  the  impulse,  and 
therefore  of  the  output  of  blood  from  the  heart. 

If  the  driving  force  exerted  on  the  blood  by  the  heart  were 
continuous  and  uniform,  the  elasticity  of  the  system  would  have  no 
effect  other  than  to  produce  a  greater  or  less  degree  of  vascular 
dilatation,  in  proportion  with  the  force  of  the  prevailing  pressure ; 
but  the  blood-flow  would  remain  stationary  in  every  part,  and  be 
governed  by  the  same  laws  as  in  the  system  of  rigid  tubes.  If  in 
the  latter  the  driving  force  is  not  continuous  but  intermittent,  the 
current  through  the  tubes  and  the  outflow  at  the  end  of  the  system 
are  also  intermittent.  But  when  the  impulsive  force  works  inter- 
mittently in  a  system  of  elastic  tubes,  then,  during  the  impulse,  a 
portion  only  of  that  force  will  be  employed  in  propelling  the  fluid 
along  the  tubes ;  while  the  other  portion,  by  which  the  tubes  are 
dilated,  will  be  stored  up  in  the  form  of  elastic  tension,  and  given 
back  by  the  reaction  at  the  close  of  the  impulse.  Owing 
to  this  elasticity,  the  current  which  is  intermittent  at  the 
head  of  the  system  becomes  remittent  during  its  course,  till  at  the 
outflow  or  extremity  of  the  system  it  is  continuous  and  uniform. 

Marey's  experimental  schema  is  the  best  way  of  demonstrating 
the  effect  of  the  elasticity  of  the  vessel  walls  in  regulating  the 


vin       BLOOD-STKEAM :   MOVEMENT  IN  VESSELS       239 

blood -tiow  and  making  it  continuous.  A  large  Mariotte  flask 
raised  to  a  certain  height  by  a  wooden  block  is  employed,  having 
an  orifice  at  its  base  opening  into  a  flexible  lead  tube,  divided  into 
two  branches.  One  of  these  is  attached  by  a  short  rubber  junction 
to  a  long  narrow  glass  tube,  somewhat  pointed  at  the  end ;  the  other 
branch  is  continued  as  a  fine  tube  of  elastic  rubber  of  the  same 
diameter  as  the  glass  tube,  ending  in  a  short  glass  mouthpiece 
with  the  same  aperture  of  outflow  as  the  other  (Fig.  90).  When 
•the  tap  is  opened  and  the  water  contained  in  the  Mariotte  flask  is 
allowed  to  flow  out  through  the  two  tubes,  one  having  rigid,  the 
other  elastic  walls,  the  amount  of  fluid  escaping  simultaneously 


FIG.  90. — Mosso's  apparatus  for  demonstrating  the  effect  of  an  intermittent  flow  on  two  tubes, 
one  having  rigid,  the  other  elastic,  walls. 

from  the  two  tubes  will  be  equal,  since  the  two  orifices  are  equal  in 
diameter.  This  proves  that  when  hydrostatic  pressure  is  continuous 
and  uniform,  elastic  tubes  act  like  rigid  tubes.  But  if  the  action 
of  hydrostatic  pressure  is  rendered  intermittent  by  rhythmically 
opening  and  closing  the  compression  lever  carried  by  the  apparatus, 
as  shown  in  the  figure,  it  will  be  seen  that  the  glass  tube  expels 
the  water  intermittently  from  its  mouth,  while  the  elastic  tube 
yields  a  continuous  and  regular  flow.  Uniformity  of  current  is 
thus  shown  to  be  due  to  the  elasticity  of  the  tube. 

The  impulse  imparted  to  the  blood  by  the  elastic  reaction  of  the 
vessels  is  not  a  new  force  added  to  that  developed  by  the  heart 
during  its  systolic  output ;  it  is  only  the  restitution  of  that  part  of 
the  impulsive  force  of  the  heart  which  was  applied  to  throwing  the 
arteries  into  elastic  tension  (Berard).  Yet  even  if  the  elasticity  of 
the  arteries  adds  nothing  to  the  sum  of  the  driving  force  of  the 
heart,  it  still  diminishes  the  sum  of  the  resistance  opposed  to  the . 


240  PHYSIOLOGY  CHAP. 

entrance  of  the  blood  into  the  arteries.  In  this  way  a  portion  of 
the  mechanical  work  of  the  heart,  which  would  otherwise  be  lost 
in  overcoming  the  great  resistance  which  the  blood  would  meet  in 
making  its  way  into  the  arteries,  if  these  were  rigid  tubes,  is  saved 
and  utilised.  By  the  same  experimental  schema  Marey  was  easily 
able  to  demonstrate  that  the  amount  of  fluid  passing  through  an 
elastic  tube  is  considerably  greater  than  that  flowing  in  the  same 
time  through  a  rigid  pipe,  when  fluid  is  driven  through  both 
intermittently. 

Another  invariable  result  of  the  intermittent  character  of  the 
driving  force  exerted  by  the  heart  on  the  arterial  blood  is  the 
production  of  a  positive  wave  at  each  systole,  i.e.  a  dilatation  which 
is  rapidly  propagated  in  a  diminishing  degree  from  the  larger  to 
the  smaller  arteries,  and  usually  dies  out  at  the  threshold  of  the 
capillary  network.  This  positive  wave  gives  rise  to  the  arterial 
pulse,  and  is  accordingly  known  as  the  spliygmic  or  pulse  wave. 
The  rapid  transmission  of  the  pulse  wave  through  the  arteries 
coincides  with  a  momentary  rise  of  blood  pressure  perceptible 
to  the  touch,  and  a  momentary  acceleration  of  the  blood-flow, 
which,  as  we  have  seen,  can  be  directly  observed  under  the 
microscope. 

E.  H.  Weber  (1850)  was  the  first  to  make  a  thorough  experi- 
mental study  of  the  laws  of  wave  movement.  For  our  purpose  it 
will  be  sufficient  to  consider  the  fundamental  principles  on  which 
the  complex  and  delicate  mechanism  of  the  production  of  this  wave 
depend.  At  each  outflow  of  blood  from  the  ventricles,  the  walls 
of  the  first  section  of  the  arteries  expand  in  consequence  of  the 
sudden  impact,  and  then  by  elastic  reaction  produce  the  dilatation 
of  the  succeeding  sections  by  exerting  pressure  on  the  blood  with 
which  they  are  filled.  This  elastic  transmission  of  the  wave  is 
repeated  in  the  next  section,  and  so  on.  Thus,  it  is  the  blood 
expelled  from  the  heart  which  causes  the  wave-like  dilatation  of 
the  vessel  walls,  while  the  elastic  reaction  of  the  walls  consequent 
on  this  dilatation  propagates  the  wave. 

The  gradual  diminution  of  the  wave  in  its  course  through  the 
arteries  until  it  disappears  at  the  capillary  threshold  is  an  effect 
of  the  growing  resistance  which  it  encounters  at  each  ramification 
of  the  vessels.  The  amplitude  of  the  wave  decreases  by  the  same 
laws  as  the  average  pressure  in  the  arteries. 

The  velocity  of  transmission  of  the  wave  depends  on  the  specific 
gravity  of  the  fluid,  on  the  diameter  of  the  vessels,  on  the  thickness 
of  the  vessel  walls,  and  on  its  elastic  coefficient.  According  to 
Moens,  it  is  inversely  proportional  to  the  square  root  of  the  specific 
gravity  of  the  fluid  and  to  the  internal  diameter  of  the  vessel,  and 
directly  proportional  to  the  square  root  of  the  thickness  of  the 
walls,  and  their  coefficient  of  elasticity. 

By  means  of  the  graphic  method  it  is  possible  to  study  every 


viii       BLOOD-STEEAM :   MOVEMENT  IN  VESSELS       241 

detail  of  the  propagation  of  the  pulse -wave  in  elastic  tubes. 
Besides  the  classical  researches  of  E.  H.  Weber  (1850),  we  have 
the  observations  of  Bonders  (1859),  Marey  (1875),  and  Moens 
(1880).  In  rubber  tubes  the  rate  of  propagation  of  the  wave 
varies,  according  to  different  observations,  from  10  to  18  m.  per 
second. 

In  an  elastic  tube,  thrown  into  tension  by  a  fluid,  and  closed 
at  both  ends,  it  is  possible  to  evoke  negative  as  well  as  positive 
'waves,  generated  not  by  the  sudden  rise,  but  by  the  sudden  fall  of 
pressure.  It  is  only  necessary  to  let  a  small  quantity  of  fluid 
escape  suddenly  from  one  end,  or,  after  compressing  the  tube  at  one 
point,  suddenly  to  release  the  compression,  in  order  to  produce  the 
transmission  of  a  wave,  represented  not  by  a  dilatation  but  by  an 
undulatory  depression.  The  velocity  of  propagation  of  the  negative 
wave  is  practically  the  same  as  that  of  the  positive  wave,  and 
essentially  obeys  the  same  law. 

When  the  rubber  tube  in  which  the  positive  or  negative  wave 
is  produced  is  not  so  unduly  long  that  the  wave  has  died  out  at 
the  extreme  end,  the  first  wave  propagated  through  the  tube  gives 
rise  to  a  second  reflex  wave,  which  traverses  the  entire  tube  in  the 
opposite  direction  and  interferes  with  the  primary  wave,  since 
it  has  the  same  velocity  of  transmission. 

In  elastic  tubes  which  branch  like  the  arterial  system,  the 
waves  generated  in  the  principal  vessel'  extend  to  all  the  com- 
municating branches,  and  at  the  points  at  which  the  vessels  branch, 
where  there  is  a  sudden  rise  of  resistance,  there  is  invariably  a 
formation  of  reflex  waves.  These  reflex  waves  are,  however,  lost 
when  they  reach  the  main  vessel,  which  in  consequence  of  its 
capacity  and  the  great  elasticity  of  its  walls  acts  as  a  kind  of 
extinguisher  to  the  small  waves  reflected  from  the  secondary 
vessels.  The  aorta  must  act  in  this  way  in  regard  to  the  reflex 
waves  from  the  bifurcation  points  of  all  the  other  arteries 
(Marey). 

Having  thus  discussed  the  general  laws  of  pressure,  circulatory 
velocity,  and  pulse-wave  in  the  arteries,  we  must  next  consider 
the  most  important  data  established  by  the  study  of  these  three 
complex  phenomena. 

IV.  The  idea  of  measuring  the  blood  pressure  in  the  arteries 
originated  with  Stephen  Hales  (1733).  He  connected  the  artery 
of  a  horse  with  a  long  glass  tube  in  order  to  see  the  height  to 
which  the  blood  would  rise.  In  this  way  he  ascertained  that  the 
arterial  pressure  was  equal  to  a  column  of  blood  of  8  to  9  feet.  He 
further  noted  that  the  height  of  the  column  of  blood  in  the 
tube  oscillated  with  the  cardiac  systole.  Poiseuille  (1828)  replaced 
Hales'  piezometer  by  a  U-shaped  mercury  manometer,  which  was 
a  great  advance  in  practical  method.  To  this  Ludwig  (1847) 
added  a  float  provided  with  a  pen,  which  records  every  variation 

VOL.  i  R 


242 


PHYSIOLOGY 


CHAP. 


of  the  mercury  column  on  a  rotating  cylinder.  This  is  another 
immense  advance,  as  the  recording  manometer  was  the  first 
application  £>f  the  automatic  graphic  method,  which  has  since 
been  employed  in  the  most  various  directions,  and  has  rendered 
signal  service  to  physiology.  (Fig.  91 ;  and  Fig.  68,  p.  207.) 


FIG.  91. —  Lud wig's  kymograph.  (Baltzar's  type.)  The  movements  of  the  drum  are  rendered 
uniform  by  the  clockwork  of  a  Foucault  regulator.  The  velocity  of  rotation  is  altered  either 
by  pushing  the  little  wheel  on  the  axis  of  the  drum  nearer  to  or  farther  from  the  centre 
of  the  vertical  metal  disc,  which  drives  the  drum  by  simple  friction,  or  by  adjusting  the 
clockwork  of  the  regulator. 

Ludwig's  writing  manometer  or  Kymograph  is  the  classic 
instrument  by  which  the  absolute  value  of  the  average  blood  pressure 
of  any  artery  can  be  directly  obtained  under  natural  conditions. 
An  anti- coagulant  alkaline  or  peptone  solution  is  introduced 
between  the  blood  and  the  mercury.  If  the  manometer  is  con- 
nected by  a  T-cannula  with  the  artery,  the  flow  of  blood  through 
the  vessel  is  not  interrupted,  and  the  resulting  value  gives 
the  lateral  pressure  obtaining  in  the  branch  vessel.  For  greater 


vni       BLOOD-STKEAM :   MOVEMENT  IN  VESSELS      243 

convenience,  however,  it  is  customary  to  join  the  artery  to  the 
manometer  by  a  simple  cannula,  ligatured  to  the  central  side  of 
the  artery,  so  that  the  vessel  is  occluded.  In  this  case  the  height  of 
the  manometer  column  of  course  expresses  the  lateral  pressure  in 
the  arterial  trunk  from  which  the  occluded  vessel  sprang.  The 
cannula  may  also  be  introduced  in  a  peripheral,  instead  of  central, 
direction  in  the  artery.  In  this  case  the  manometer  measures  the 
pressure  either  in  the  capillary  network  or  in  the  other  arterial 
branches  with  which  the  artery,  to  which  the  cannula  is  peri- 
pherally connected,  anastomoses.  For  instance,  a  manometer 
connected  by  a  cannula  with  the  central  side  of  the  dog's  carotid 
measures  the  lateral  pressure  in  the  aoria  ;  if,  on  the  other  hand, 
the  cannula  is  connected  with  the  peripheral  side  of  the  same 
artery,  the  pressure  that  obtains  in  the  so-called  Circle  of  Willis 
will  be  obtained.  In  the  first  case,  the  pressure,  according  to 


FIG.  92. — Tracing  of  arterial  pressure  in  dog's  carotid,  recorded  by  Lud  wig's  kymograph. 

(Marey.) 

Steiner,  may  reach  a  value  of  214  mm.  Hg ;  in  the  second,  a 
pressure  of  only  154  mm.  Hg  results.  The  first  value  represents 
the  lateral  pressure  that  prevails  in  the  trunk  of  the  aorta  at  the 
origin  of  the  carotid ;  the  second,  the  pressure  in  the  arterial  Circle 
of  Willis,  which  communicates  directly  with  the  peripheral  trunk 
of  the  carotid. 

As  can  be  seen  in  Fig.  92,  the  tracings  recorded  with  Lud  wig's 
manometer  exhibit  small  oscillations  corresponding  with  the  single 
cardiac  systoles,  and  more  ample  and  less  steep  oscillations  which 
correspond  to  the  respiratory  movements. 

The  latter  will  be  considered  in  relation  to  the  mechanics  of 
respiration ;  as  regards  the  pulsatory  oscillations  it  must  be  noted 
that  the  mercury,  owing  to  inertia,  is  incapable  of  faithfully 
recording  the  rapid  variations  of  arterial  pressure  produced  by 
each  wave  of  blood  expelled  from  .the  heart,  so  that  Ludwig's 
instrument  is  the  least  fitted  for  the  study  of  the  form  of  the 
pulse-wave.  Since  this  instrument  is  intended  to  determine  the 
value  of  the  average  blood  pressure,  the  pulsatory  oscillations  are 
a  superfluous  complication  which  can  easily  be  excluded  by  a 
constriction  in  the  manometer  at  one  point,  as  proposed  by 


244  PHYSIOLOGY  CHAP. 

Setschenow,  which  prevents  the  mercury  from  making  any  rapid 
movement.  In  the  manometer  represented  in  Fig.  68,  p.  207,  this 
is  easily  effected  by  adjusting  the  screw  placed  at  its  lower  end 
to  the  required  point.  The  mercury  column  is  then  practically 
immobile  between  the  highest  and  lowest  points  of  the  pulsatory 
oscillations,  and  the  apparatus  merely  records  the  average  blood 
pressure. 

In  order  to  obtain  as  true  a  record  as  possible  of  even  the 
most  rapid  oscillations  of  blood  pressure,  the  elastic  manometer  or 
tonometer  was  invented,  in  which  the  mercury  mass  is  replaced  by 
a  spring  or  other  elastic  body,  having  but  a  small  mass,  and  being, 
therefore,  more  free  from  the  errors  due  to  inertia,  and  better 
adapted  to  follow  accurately  the  finer  details  of  the  pulsatory 
oscillations  of  pressure.  The  history  of  the  modifications  and 
gradual  perfecting  of  the  elastic  manometer  are  of  merely  technical 
interest.  We  must  confine  ourselves  to  mentioning  the  hollow 
spring  manometer  of  A.  Fick  (1864),  constructed  on  the  same 
principle  as  Bourdon's  metal  manometer,  employed  in  steam- 
engines,  and  the  metal  manometer  of  Marey,  which  is  constructed 
on  the  principle  of  the  aneroid  barometer.  In  1885  Fick  invented 
another  flat  spring  manometer,  which  is  simpler  and  more  sensitive 
than  the  preceding.  The  entire  apparatus  is  reduced  to  a  slender 
tube  ending  in  a  small  capsule,  closed  by  a  rubber  membrane, 
capable  of  small  excursions  which  are  transmitted  to  a  flat  steel 
spring.  By  this  method  it  is  possible  to  reduce  the  movements  of 
the  column  of  fluid  in  the  tube  connected  with  the  artery  to  a 
minimum,  which  facilitates  the  transmission  of  the  more  rapid 
oscillations,  and  avoids  the  inconvenience  of  coagulated  blood  at 
the  point  of  the  cannula.  In  order  to  magnify  the  oscillations  of 
pressure  transmitted  to  the  spring,  and  to  record  them  on  a 
rotating  drum,  it  is  fitted  with  a  long,  light  lever  made  from  a 
straw.  Hiirthle  perfected  this  manometer  of  Fick's  by  some 
accessory  contrivances,  which  made  its  application  easier  and  more 
certain,  and  confined  the  fluid  between  artery  and  manometer  to 
'the  lowest  possible  minimum  in  order  to  transmit  the  variations 
of  pressure  more  rapidly  and  faithfully.  Of  course  both  Fick's 
manometer  and  that  of  Hiirthle  must  be  empirically  graduated 
by  a  mercury  manometer  in  order  to  show  absolute  pressures. 

Still  better  than  a  steel  spring,  however,  for  obtaining  true 
curves  of  the  pulsatory  oscillations  of  pressure,  is  the  tonometer 
formed  of  elastic  guttapercha,  the  simplest  type  of  which  is  Marey 
and  Chauveau's  sphygmoscope  (Fig.  66,  p.  205)  in  connection 
with  their  writing  tambour  (Fig.  63,  p.  201).  In  order  to  diminish 
the  mass  of  fluid  communicating  with  the  artery,  Hiirthle  reduced 
Marey 's  tambour  to  a  small  capsule,  covered  with  a  resistent 
rubber  membrane  ;  its  excursions  were  magnified  by  a  long  and 
very  light  lever,  while  the  capsule,  by  omitting  the  sphygmoscope,. 


viii       BLOOD-STKEAM :   MOVEMENT  IN  VESSELS       245 

was  placed  in  direct  connection  with  the  artery.  This  is  Hiirthle's 
rubber  manometer.  Since  the  rubber  membrane  easily  perishes, 
Gad  substituted  for  it  a  thin  metal  plate.  Finally,  v.  Frey 
gave  the  most  practical  form  and  shape  to  the  entire  apparatus, 
combining  the  maximum  of  sensitiveness  with  stability  and 
permanence.  He  called  it  a  meted  tonograph  (Fig.  93). 

More  recently  (1904)  Ducceschi  has  described  a  still  simpler 
method,  by  which  the  tracings  of  the  normal  blood  pressure  in  the 
carotid  of  dogs  and  rabbits  can  be  recorded.  After  isolating  a 
sufficiently  long  tract  of  this  artery  in  the  neck,  he  divided  it 
between  two  ligatures,  putting  the  central  end  in  direct  com- 
munication with  the  isotonic  lever  of  a  myograph  by  means  of  an 
inextensible  thread,  and  counterbalancing  the  tension  with  an 
adequate  weight.  In  principle  this  method  is  the  same  as  that 
employed  by  En- 
gelmann  to  record 
the  pulsations  of 
the-  frog's  heart 
(see  next  chapter), 
and  its  author  gave 
it  the  name  of 
method  of  suspen- 
sion of  the  artery, 
just  as  Engelmann 

p  n  1 1  P  rl  TIIG  f  Vi  P  Fl°-  93.— Von  Frey's  metal  tonograpli,  in  which  the  rubber  membrane 
cailea  iff  replaced  by  a  metal  plate. 

method  of  suspen- 
sion of  the  heart.  It  is  evident  that  the  pressure  of  the  blood, 
exerted  on  the  closed  trunk  of  the  carotid,  must  distend  it  in 
correspondence  with  the  average  pressure  and  the  rhythmical 
oscillations  due  to  the  rhythmical  beat  of  the  heart  (longitudinal 
locomotion  and  arterial  pulse). 

Since  these  methods  all  involve  the  opening  of  an  artery,  and 
introduction  of  a  cannula,  they  are  only  practicable  on  man  in 
certain  surgical  operations  (amputations)  and  other  conditions 
more  or  less  removed  from  a  physiological  state.  Methods  have 
accordingly  been  invented  by  which  it  is  possible  to  determine 
blood  pressure  without  any  surgical  operation,  and  these  can 
therefore  be  applied  to  man.  Vierordt  (1855)  was  the  first  who 
conceived  the  idea  of  measuring  the  blood  pressure  in  an  artery 
indirectly,  by  ascertaining  the  weight  required  to  suppress  the 
pulsations.  Waldenburg,  Potain,  Talma,  Koy  and  Brown 
attempted  the  solution  of  the  same  problem.  The  sphygmomano- 
meter  of  v.  Basch  (1876)  is  a  small  instrument  designed  for  this 
purpose,  which  has  found  wide  acceptance  with  clinicians  on 
account  of  its  easy  applicability.  It  consists  of  a  rubber  finger- 
stall filled  with  water,  by  which  the  radial  or  temporal  artery  i . 
compressed.  The  finger-stall  communicates  by  a  rubber  tube  with 


246 


PHYSIOLOGY 


CHAP. 


a  metal  manometer,  the  indicator  of  which  shows  the  pressure 
exercised  on  the  artery.  When  the  indicator  no  longer  shows 
pulse  -  waves  in  the  compressed  artery,  the  internal  pressure, 
according  to  v.  Basch,  must  (at  any  rate  approximately)  be  equal 
to  the  external  compression.  Tigerstedt  rightly  pointed  out  the 
untrustworthy  character  of  the  values  obtained  by  this  method. 
In  spite  of  the  improvements  introduced  by  Eabinowitz  (1881) 
and  Potain  (1889)  in  the  apparatus,  and  adopted  by  von  Basch  in 
the  latest  model  of  his  sphygmomanometer  (1890),  and  notwith- 
standing the  many  control  experiments  carried  out  by  various 


FIG.  94. —  Tracings  of  pulsatory  oscillations  in  volume  of  forearm,  recorded  with  Marey's 
sphygmomanometer.  Shows  the  variations  under  the  influence  of  increasing  external 
pressure,  as  indicated  in  cm.  Hg  at  the  side  of  each  tracing.  (Marey.) 

authors  upon  animals  (which  show  that  while  the  pressure  values 
obtained  from  this  instrument  are  unreliable,  they  still  yield 
results  comparable  inter  se  on  the  same  individual),  there  are 
certain  obvious  drawbacks  to  its  practical  application  to  man 
which  are  not  easily  removed,  and  which  render  it  untrustworthy. 
The  results  may  vary  considerably  in  different  cases,  according  to 
the  depth  of  the  paniculus  adiposus,  the  development  of  the 
muscles,  the  arrangement  and  normal  or  sclerotic  state  of  the 
arterial  walls,  and  in  particular  the  tension  of  the  aponeurotic 
fascia  which  cover  the  arteries  investigated,  and  more  or  less  hinder 
their  compression. 

The  investigations  initiated  by  Marey  (1876),  resumed  in  1878, 
and  continued  in  Italy  in  1895  by  Mosso,  were  more  successful. 


vin       BLOOD-STEEAM :   MOVEMENT  IN  VESSELS       247 


Marey's  sphygmomanometric  method  consists  in  applying  a 
variable  external  counter-pressure  not  to  a  limited  point  of  an 
artery,  but  to  the  whole  surface  of  a  limb.  He  introduced  the 
forearm  into  a  cylindrical  vessel  closed  by  a  rubber  ring,  which 
was  filled  under  easily  adjustable  pressure  with  water,  and 
connected  with  a  recording  manometer,  and  then  took  a  tracing 
of  the  total  pulsations  of  all  the  arteries  of  the  forearm.  He  saw 
that  with  gradual  increase  of  hydrostatic  pressure  within  the 
cylinder,  the  pulsations  increased  during  a  first  period,  and  then 
diminished  in  a  second,  till  they  ceased  entirely.  In  the  tracings 
of  Fig.  94  it  can  be  seen  that  the  pulsations  attain 
their  maximal  excursion  when  the  counter-pressure 
on  the  forearm  reaches  8  cm.  Hg ;  they  then  gradu- 
ally diminish,  and  almost  entirely  disappear  at  a 
counter-pressure  of  19*5  cm.  Hg. 

In  a  second  series  of  experiments  Marey,  in  order 
to  make  his  method  more  practicable,  gave  up  the 
pressure  on  the  whole  forearm,  and  confined  himself 
to  one  finger  of  the  hand,  as  seen  in  the  apparatus 
of  Fig.  95.  In  order  to  make  the  pulsations  of  the 


FIG.  95. — Marey's  sphygmomanometer.  It  consists  of  a  glass  holder  M,  which  is  completely  closed 
after  introducing  the  fore-finger,  and  communicates  on  the  one  hand  with  a  capillary  mercury 
manometer  b,  on  the  other  with  a  stout  bag  c,  which  is  gradually  compressed  by  a  screw.  The 
whole  apparatus  should  be  filled  with  water,  care  being  taken  to  avoid  air-bubbles. 

digital  arteries  more  conspicuous,  he  employed  a  mercury  mano- 
meter of  ^  mm.  diameter,  and  limited  himself  to  reading  the 
maximal  and  minimal  values  of  the  pulsatory  oscillations  on  the 
scale.  This  method  again  confirmed  the  preceding  observation,  to 
the  effect  that  the  pulsations,  with  increase  of  counter-pressure, 
are  greater  at  first,  and  subsequently  diminish  and  tend  to  die  out. 
But  he  also  found  that  it  was  very  difficult  to  obliterate  them 
completely,  even  when  the  counter-pressure  reached  a  height  of 
28-30  cm.  Hg,  i.e.  a  value  which  is  certainly  higher  than  the 
pressure  exerted  by  the  blood  on  the  arteries  of  the  fingers. 
According  to  Marey,  however,  the  value  of  his  method  lies  in  the 
determination  of  the  counter-pressure  with  which  the  most  ample 
oscillations  of  the  mercury  column  are  obtained.  "At  that  moment," 


248  PHYSIOLOGY  CHAP. 

he  says,  "  we  learn  theoretically  that  the  vessels  of  the  immersed 
limb  are  wholly  relaxed,  and  that  their  walls  fluctuate  as  it  were 
indifferently  between  the  internal  pressure  of  the  blood  and  the 
external  pressure  of  the  water.  The  pressure  of  the  blood,  there- 
fore, acts  as  though  it  were  exerted  directly  upon  the  manometer." 
This  is  as  much  as  to  say  that  we  then  obtain  the  true  measure  of 
the  lateral  pressure  exerted  by  the  blood  upon  the  arteries  of  the 
finger.  The  arterial  walls  at  that  time  must  be  in  a  state  of  elastic 
equilibrium,  since  the  internal  force  which  makes  for  their  dis- 
tension is  completely  counterbalanced  by  the  external  force  which 
makes  for  their  compression.  If  this  criterion  is  applied  to  the 
results  shown  in  Fig.  94,  the  average  pressure  of  the  arteries  of  the 
forearm  in  man  is  found  equal  to  8  cm.  Hg,  since  the  pulsations 
reach  their  maximal  amplitude  when  a  counter-pressure  of  8  cm. 
Hg  is  put  upon  them. 

Mosso  continued  and  developed  these  investigations  of  Marey. 
His  sphygmomanometer  is  a  modification  of  that  shown  in  the 
previous  figure.  He  makes  the  counter -pressure  act  on  four 
fingers  instead  of  on  one,  in  order  to  obtain  the  total  pulsations  of  a 
larger  number  of  arteries,  and  to  record  the  tracings  with  a  Ludwig's 
mercury  manometer.  The  following  tracings,  obtained  by  Mosso 
and  Colombo,  are  very  instructive,  the  effects  of  various  degrees 
of  compression  of  the  four  fingers  under  normal  conditions  being 
compared  with  the  tracings  obtained  from  the  same  person  after 
a  warm  bath  (Fig.  96). 

As  might  be  expected,  the  average  pressure  sinks  on  account 
of  the  relaxation  of  the  vessels  due  to  the  warm  bath,  and  falls  to 
20  mm.  Hg.  At  the  same  time  the  height  of  the  pulsations  after 
the  bath  increases  considerably,  showing  that  they  do  not  depend 
on  the  internal  pressure  of  the  blood,  but  are  in  inverse  ratio  with 
the  degree  of  tonic  contraction  of  the  vessels.  Evidence  for  this  is 
found  in  the  fact  that  when  the  vessels  of  the  fingers  are  strongly 
contracted  (as  often  happens  in  winter),  it  is  impossible  to  obtain 
the  slightest  sign  of  pulsation  with  Mosso's  sphygmomanometer. 
This  is  a  disadvantage  which  renders  the  instrument  applicable 
only  to  a  limited  number  of  persons,  and  which  is  avoided  by 
returning  to  the  original  method  of  Marey,  i.e.  that  of  applying 
compression  to  the  whole  forearm. 

Starting  from  Marey's  original  method,  Hiirthle  (1896)  intro- 
duced some  interesting  modifications  which  deserve  notice. 

Both  in  Marey's  and  in  Mosso's  apparatus  it  is  necessary  in 
measuring  the  lateral  pressure  prevailing  in  the  arteries  of  the  part 
of  the  body  examined,  to  increase  or  lower  the  external  counter- 
pressure  repeatedly,  in  order  to  discover  at  what  strength  of  counter- 
pressure  the  maximal  pulsations  are  obtained.  With  Hlirthle's  ap- 
paratus, on  the  contrary,  the  observation  is  continuous,  and  there  is  no 
need  to  vary  the  counter-pressure  applied  at  the  outset  to  the  forearm. 


vni       BLOOD-STEEAM:   MOVEMENT  IN  VESSELS       249 

He  starts  with  the  production   of  artificial  anaemia   by  an 


ol 

|« 

fi 

I! 


II 


•a  3 


fi» 

=Ȥi 

•<  s  r 


-171  tc  ® 

' 


. 

I 


Esmarch's  bandage  in  the  forearm  and  part  of  the  upper  arm,  and 
ties  a  ligature  round  the  latter.     He  then  introduces  the  anaemic 


250  PHYSIOLOGY  CHAP. 

extremity,  as  far  as  half  the  forearm,  into  a  glass  cylinder,  connected 
on  one  side  with  a  pressure  bottle,  on  the  other  with  his  spring 
manometer.  An  ingenious  apparatus  that  is  absolutely  air-tight 
fixes  the  end  of  the  cylinder  to  the  forearm.  After  the  cylinder 
has  been  filled  with  water  and  the  connection  with  the  pressure 
bottle  closed,  the  ligature  is  taken  off;  the  blood  from  the  artery 
then  flows  into  the  limb  and  drives  some  of  the  water  against  the 
manometer,  which  records  a  pressure  equivalent  to  that  exerted  by 
the  blood  streaming  into  the  artery.  Since  the  spring  manometer 
permits  only  small  excursions,  the  quantity  of  blood  entering  the 
artery  of  that  part  of  the  arm  which  is  enclosed  in  the  cylinder 
will  also  be  small.  Hiirthle  takes  it  to  be  not  more  than  10  c.c., 
which  is  certainly  not  sufficient  to  restore  circulation  in  the  vessels 
of  the  limb.  He  therefore  concludes  that  the  values  recorded  by 
his  apparatus  represent^  not  the  simple  lateral  pressure,  but  the 
total  arterial  pressure  (total  head)  which  would  obtain  if  the  large 
artery  of  the  forearm  were  opened,  and  directly  connected  with 
the  manometer. 

Hiirthle  has  not,  up  to  the  present,  published  any  control 
experiments  that  justify  his  conclusions,  and  there  are  good 
reasons  for  doubting  whether  he  has  really  succeeded  in  completely 
obliterating  all  the  vessels  of  the  forearm,  so  as  to  interrupt 
the  circulation  in  the  vessels  of  the  interosseous  space.  The 
external  pressure  is  not  readily  transmitted  to  this  space,  since  the 
two  bones  are  connected  by  strong  aponeuroses,  which  make  this 
cavity  a  box  with  rigid  walls  that  yield  little  to  pressure  greater 
even  than  that  of  the  largest  arteries.  It  is  therefore  probable, 
in  consequence  of  the  incomplete  stoppage  of  the  circulation,  that 
Hlirthle's  apparatus  does  not  register  the  total  head,  but  merely  a 
pressure  head  which  is  not  of  the  same  value  as  the  lateral  pressure 
of  the  blood  normally  circulating  in  the  vessels  of  the  forearm,  but 
increases  in  proportion  with  the  sudden  restriction  of  current-bed 
in  the  greater  part  of  the  lirnb  that  is  under  investigation. 

From  the  clinical  standpoint  these  methods  of  Marey,  Mosso, 
and  Hiirthle  involve  too  complicated  an  apparatus,  requiring  no 
little  skill  on  the  part  of  operator  as  well  as  patient,  to  ensure 
success.  Moreover,  they  only  determine  the  lateral  pressure  in 
arteries  too  small  and  too  remote  from  the  heart  to  give  the 
physician  any  adequate  expression  of  the  energy  with  which  the 
heart  is  acting  under  various  morbid  conditions. 

Eiva-Kocci  (1896)  accordingly  invented  a  simple  and  easily 
applied  sphygmomanometer,  which  measures  by  the  manometer 
the  external  counter-pressure  required  to  block  the  progress  of  the 
pulse-wave  in  one  of  the  larger  branches  of  the  aorta,  e.g.  in  the 
brachial  artery.  The  measurements  obtained  with  this  instrument, 
which  express  the  total  pressure  head  (i.e.  the  lateral  pressure  plus 
the  velocity  head)  in  the  brachial  artery,  express  the  values  of  the 


viii       BLOOD-STEEAM :   MOVEMENT  IN  VESSELS       251 


lateral  pressure  that  prevails  in  the  aorta  or  innominate  artery, 
according  as  the  apparatus  is  applied  to  the  left  or  to  the 
right  arm. 

Kiva-Eocci's  sphygmomanometer  is  an  ingenious  modification 
of  the  method  of  v.  Basch.  The  elastic  finger-stall  is  replaced  by 
a  hollow  rubber  ring  (made  inextensible  by  a  cloth  cover)  which 
fits  round  the  arm  and  is  connected  with  a  mercury  manometer 
(Fig.  97).  Air  is  then  blown  into  the  hollow  ring  by  an  ordinary 
spray  bellows,  which  becomes  inflated  and  compresses  all  the 
vessels  of  the  limb,  while  the  mercury  rises  in  the  tube  of  the 
manometer.  If  more  air  is  gradually  forced  in,  so  that  the 
mercury  rises  evenly,  there 
comes  a  moment  at  which 
the  radial  pulse  disappears. 
The  height  of  the  mercury 
column  at  that  moment 
represents  the  total  head  of 
pressure  supported  by  the 
brachial  artery  during  the 
interruption  of  the  circu- 
lation in  the  arm,  which 
value  approximates  to  that 
of  the  lateral  pressure  in 
the  aorta,  as  demonstrated 
by  experiments  with  arti- 
ficial circulation  in  rubber 
tubes,  or  in  the  brachial 


arteries       of 
body,   as    well 
periments     On 

P 
arterieS         OI 

rabbits. 


the       dead 
by   ex- 


as 


the 
ClOgS 


Crural    FIG.  97.  —  Riva-Rocci's  sphygmomanometer.    a,  Hollow 


and 


rubber  ring  covered  with  silk  ;  m,  mercury  inano- 
meter  with  only  one  arm  ;  i,  double  rubber  bellows. 


As  the  sphygmomanometer  of  Eiva-Eocci  is  applied  to  the 
upper  arm,  which  has  only  one  central  bone,  the  muscles,  when 
fully  relaxed,  behave  exactly  like  a  fluid,  and  convey  the  pressure 
of  the  elastic  ring  perfectly  to  all  the  vessels  of  the  upper  arm,  as 
was  not  the  case  when  the  apparatus  was  applied  to  the  forearm. 
The  chief  detects  of  v.  Basch's  sphygmomanometer  thus  seem  to 
be  excluded. 

In  order  to  obtain  utilisable  values  with  the  Riva-Rocci  apparatus,  it  is 
essential  that  the  subject  whose  pressure  is  to  be  measured  should  be 
absolutely  quiescent.  In  this  way  only  can  the  value  of  the  individual  minimal 
pressure  be  obtained,  uninfluenced  by  the  disturbances  produced  by  emotional 
influences,  which  vary  to  a  considerable  extent  in  the  same  person,  with  the 
same  stimulus.  The  armlet  is  fastened  preferably  to  the  middle  of  the  right 
arm  by  means  of  the  ligature  attached  from  behind  to  the  lower  part  of  the 
arm,  so  that  it  is  applied  to  it  like  a  flat  bandage. 

The  forearm  is  bent  towards  the  upper  arm,  care  being  taken  that  all  the 


252 


PHYSIOLOGY 


CHAP. 


muscles  of  the  latter,  especially  tlie  biceps,  are  entirely  relaxed.  With  one 
hand  the  operator  feels  the  brachial  or  radial  pulse  at  the  bend  of  the  elbow 
joint,  and  with  the  other  he  slowly  blows  in  air,  until  every  trace  of  pulse  is 
lost.  If  the  manometer  scale  is  now  read  for  the  exact  point  at  which  the 
pulse  disappeared  without  reappearing  during  maintenance  of  the  pressure, 
the  desired  pressure  value  will  be  obtained. 

Another  simple  apparatus,  easy  to  handle,  which  with  certain  modifica- 
tions is  making  its  way  like  the  preceding  into  medical  practice,  is  Gartner's 
tonometer  (1899).  This  apparatus  (Fig.  98)  to  some  extent  combines  the 
principles  of  the  methods  of  Hiirthle  and  of  Biva-Rocci.  It  also  consists  of 
a  hollow  ring,  with  an  internal  wall  of  rubber,  which  can  be  gradually 
inflated  by  an  elastic  spray  bellows,  and  communicates  on  the  other  hand 
with  a  mercury  manometer,  on  the  scale  of  which  the  pressure  values  may  be 

read.  It  is  fixed  round  one  of  the 
fingers,  and  measures  the  total 
pressure  of  the  blood  in  the  arteries 
of  that  finger.  The  method  is  as 
follows.  First,  as  in  Hiirthle's 
method,  the  phalanx  of  the  finger 
to  be  experimented  on  is  made 
anaemic,  by  applying  an  elastic 
bandage  to  the  finger  or  by  slipping 
a  rubber  ring  over  it  ;  or,  on  the 
principle  of  an  Esmarch's  bandage, 
rolling  down  from  the  point  of  the 
finger  to  the  root,  over  the  differ- 
ent joints  in  succession,  a  fine 
strip  or  tube  of,  elastic  rubber. 
The  finger  is  then  introduced  into 
the  pneumatic  ring  of  the  appara- 
tus, so  that  the  ring  embraces  the 
phalanx,  and  air  is  blown  in  from 
the  elastic  bag  by  turning  the  screw 
of  the  compressor  until  the  pres- 
sure of  the  tonometer  exceeds  that 
of  the  blood.  The  bandage  which 
FIG.  98.—  Gartner's  tonometer.  Consists  of  bellows  produced  anaemia  is  then  removed, 
(4,0ooSrn,SrrrtheW±  Sn^  ™*  the  pressure  withmthe  tone- 

a    one-armed    mercury    manometer    (m),    on    meter    Slowly    reduced     by   turning 

the  other  with  a  hollow  ring  (a)  which  slips   the  screw  that  compresses  the  elas- 
"111*"-'11*"'    tic  W  in  the  opposite  direction, 


until  the  internal  pressure  exceeds 
the  external  counter-pressure,  and  the  blood  re-enters  the  arteries  of  the 
finger  as  shown  by  the  flushing  of  the  pulp,  or  subjectively  by  the  return  of 
the  pulse.  The  value  read  at  that  moment  on  the  manometer  scale  is  equal 
to  the  total  pressure  of  the  blood  in  the  digital  arteries. 

V.  Volkmann  concluded  from  the  data  which  he  collected  in 
order  to  determine  the  variations  of  normal  blood  pressure  in 
various  species  of  animals,  that  the  height  of  pressure  is  in  no 
sort  of  ratio  with  the  size  of  the  animal.  The  lateral  pressure  in 
the  dog's  aorta,  e.g.,  fluctuates  between  130  and  180  mm.  Hg,  in 
the  rabbit  between  100  and  130  mm.  Hg,  in  the  horse  between 
150  and  200  mm.  Hg.  This  seems  paradoxical  at  first  sight,  but 
is  not  so  when  we  reflect  that  the  work  of  the  heart  depends  not 
only  upon  the  magnitude  of  resistance  or  pressure,  but  also  upon 


vin       BLOOD-STEEAM :   MOVEMENT  IN  VESSELS       253 

the  volume  of  blood  driven  by  the  heart  into  the  arteries  at  each 
systole.  Even  if  blood  pressure  in  the  horse  differs  little  from 
that  of  the  rabbit,  yet  the  horse's  heart  does  far  more  work, 
because  it  throws  a  far  greater  quantity  of  blood  into  circulation. 

The  mean  blood  pressure  in  man  cannot  differ  much  from  that 
of  the  larger  mammals.  We  may  think  of  it  as  varying  approxi- 
mately from  130  to  150  mm.  Hg,  values  which  come  very  near 
those  which  Faivre  (1850)  determined  directly  upon  the  femoral 
'and  brachial  arteries  in  amputations. 

The  values  obtained  by  Marey  and  Mosso  by  their  sphygmo- 
rnanometric  methods  reach  no  such  high  figures  (80  to  90  mm. 
Hg) ;  yet  it  must  be  remembered  that  they  only  represent  the 
average  total  pressure  of  all  the  arteries,  large  and  small,  of  the 
forearm,  or  of  the  fingers  of  the  hand. 

The  mean  arterial  pressures,  as  determined  by  Eiva  -  Eocci 
with  his  sphygmomanometer,  oscillated  in  healthy  individuals 
between  125  and  135  mm.  Hg.  They  corresponded  to  the 
greatest  total  pressure  obtained  in  the  brachial  artery  of  man 
when  a  simple  cannula  is  introduced  in  a  central  direction,  and 
connected  with  Ludwig's  kymograph.  As  we  have  said,  these 
values  represent  approximately  that  of  the  lateral  pressure  that 
prevails  in  the  aorta. 

The  blood  pressure  sinks  very  little  between  the  aorta  and  the 
larger  branches  of  the  arteries,  in  which  it  is  possible  to  introduce 
a  cannula  connected  with  a  manometer,  because  the  resistance  due 
to  the  friction  surfaces  increases  very  little.  Volkmann  gives  the 
following  data  for  dog  and  calf,  which  correspond  essentially  with 
those  obtained  by  Bernard,  Marey,  and  others : — 

Carotid        of  dog  =  172  mm.  Hg.         Carotid        of  calf  =116  mm.  Hg. 
Femoral  „     =165        „  Femoral  „       =116         „ 

Metatarsal       „     =155        „  Metatarsal       „      =   88        „ 

On  the  other  hand,  pressure  falls  rapidly  in  the  small  branches 
of  the  arteries,  where  there  are  many  ramifications,  and  in  the 
capillaries,  where  the  friction  surfaces  are  greatest.  The  values 
obtained  by  v.  Kries  with  Ludwig's  method  of  counter-pressure 
can  only  be  taken  as  approximate.  Generally  speaking,  we  may 
assume  that  pressure  in  the  capillaries  does  not  exceed  ^-f-  of 
the  aortic  pressure  (about  20-38  mm.  Hg). 

In  the  trunks  of  the  veins  nearest  the  heart,  as  in  the  in- 
nominate, subclavian,  and  jugulars,  there  is  on  an  average  a 
negative  pressure,  which  according  to  Jacobsen  may  attain  a 
value  of  -0*1  mm.  Hg,  and  is  due  to  the  aspiration  exerted  by  the 
lungs  in  consequence  of  the  elastic  tension  into  which  they  are 
thrown  during  the  expiratory  phase.  The  pressure  becomes 
positive  in  the  veins  farthest  from  the  heart  and  thorax.  Accord- 
ing to  Jacobsen  it  amounts  to  0*3  mm.  in  the  external  facial  vein 


254  PHYSIOLOGY  CHAP. 

of  sheep,  to  4'1  mm.  in  the  brachial  vein,  and  to  114  mm.  Hg  in 
the  crural  vein. 

In  the  pulmonary  circuit  the  pressure  cannot  be  determined 
directly  without  opening  the  thorax,  and  giving  artificial  respira- 
tion which  produces  a  condition  very  unlike  the  normal.  Here  we 
can  only  say  that  in  the  left  branch  of  the  pulmonary  artery 
Ludwig  found  a  pressure  =  29*6  mm.  Hg  in  the  dog ;  =  17'6  in  the 
cat;  =12  mm.  Hg  in  the  rabbit.  The  relation  between  the 
pressures  in  the  pulmonary  artery  and  the  aorta  can  be  deduced 
from  the  highest  values  which  the  pressure  reaches  during  systole 
within  the  two  ventricles.  According  to  Goltz  and  Gaule  the 
pressure  in  the  pulmonary  artery  is  to  that  in  the  aorta  as 
something  like  2  :  5. 

Blood  pressure  may  vary  very  considerably  not  only  in  different 
individuals  of  the  same  species,  but  also  in  the  same  individual  under 
different  conditions,  notwithstanding  the  regulatory  mechanism 
which  tends  to  keep  it  constant.  These  variations  depend  on 
those  of  the  three  main  factors  by  which  pressure  itself  is  normally 
determined  : — 

(a)  The  variations  in  the  energy  of  the  heart,  i.e.  in  the 
amount  of  blood  driven  in  the  time  -  unit  through  the  arterial 
system. 

(6)  The  variations  of  resistance  encountered  by  the  blood  in  its 
passage  through  the  vessels. 

(c)  The  variations  of  the  total  mass  of  blood  contained  in  the 
system. 

The  energy  of  the  heart,  and  the  work  performed  in  the  time- 
unit,  depend  both  on  the  frequency  of  its  revolutions,  and  the 
mechanical  value  of  each  of  these.  An  increase  in  the  frequency 
of  cardiac  rhythm  can  be  compensated  by  a  corresponding  diminu- 
tion in  the  mechanical  value  of  each  revolution,  and  vice  versa. 
This  mechanical  value  is  dependent  on  the  degree  of  systolic 
evacuation,  and  the  degree  of  diastolic  filling.  In  brief,  whatever 
the  determining  conditions,  an  augmentation  or  diminution  in  the 
quantity  of  blood  driven  through  from  the  heart  to  the  arteries  in 
the  unit  of  time  produces,  ceteris  paribus,  a  proportional  increase 
or  decrease  in  blood  pressure. 

Variations  in  the  resistance  of  the  vessels  exert  the  same 
influence  on  blood  pressure.  Given  the  same  energy  of  cardiac 
function,  a  greater  or  less  proportion  of  the  driving  force  will,  on 
increase  or  decrease  of  vascular  resistance,  be  expended  on  throw- 
ing the  walls  into  tension,  which  produces  a  corresponding  rise 
or  fall  of  pressure. 

Increased  vascular  resistance  can,  under  physiological  con- 
ditions, be  determined  only  by  augmentation  of  the  tonic  con- 
traction of  the  muscle  cells,  with  which  (as  we  shall  see  in  the 
next  chapter)  the  middle  layer  of  the  vessel  walls,  particularly  in 


vni       BLOOD-STEEAM :   MOVEMENT  IN  VESSELS       255 

the  small  arteries,  is  richly  provided.  The  increased  resistance  to 
the  passage  of  the  blood,  provoked  by  the  augmentation  of  vascular 
tone,  depends  both  on  the  degree  of  this  augmentation,  and  on  its 
extension  over  a  more  or  less  extensive  vascular  area. 

In  like  manner,  the  diminution  of  vascular  resistance  must,  under 
physiological  conditions,  depend  upon  a  more  or  less  pronounced 
or  diffuse  paralysis  or  diminution  of  tone  in  the  vessels.  In  the 
next  chapter  we  shall  study  the  physiological  adaptations  for 
regulating  cardiac  and  vascular  activity,  and  the  processes  by 
which  the  central  and  peripheral  variations  of  the  circulation  tend 
to  become  compensated. 

In  order  to  determine  the  dependence  of  blood  pressure  on  the 
mass  of  blood  contained  in  the  system,  it  is  obvious  that  the 
effects  on  blood  pressure  of  transfusion  and  bleeding  must  be 
considered.  This  subject  was  studied  by  Tappeiner,  and  in  an 
exhaustive  manner  by  Worin-Muller  in  1873,  in  Ludwig's  labora- 
tory. The  results  of  the  experiments  show  that  in  the  dog  during 
the  increments  in  blood  pressure  produced  by  successive  transfusions 
of  homogeneous  defibrinated  blood,  or  the  corresponding  decrement 
produced  by  successive  haemorrhages,  the  physiological  limits  vary 
very  little,  far  less  than  would  be  expected  from  the  amount  of 
blood  added  to  or  taken  from  the  system.  Further,  such  rise  or 
fall  in  arterial  pressure  is  of  very  brief  duration,  and  therefore  can 
only  be  influenced  to  a  minimal  extent  by  increase  or  diminution 
in  transudations,  and  urinary  secretions,  through  the  capillaries. 
There  must,  therefore,  be  some  compensatory  mechanism,  which 
tends  rapidly  to  restore  blood  pressure  to  the  normal,  by  producing 
a  dilatation  or  constriction  of  the  small  arteries  and  capillaries, 
which  adapts  them  even  to  very  considerable  alterations  in  the 
blood  content. 

Pawlow's  researches  (1878),  which  confirm  Worm  -  Miiller's 
observations  by  another  method,  must  also  be  noted.  When  a 
dog  was  fed  on  dry  bread  or  meat  he  found  that  blood  pressure 
fell  10  mm.  Hg  in  an  artery  of  the  thigh,  owing  to  the 
dilatation  of  the  intestinal  vessels  and  digestive  secretions.  On 
giving  the  same  dog  a  large  quantity  of  broth  he  found  no  rise  of 
blood  pressure.  There  must,  therefore,  be  some  mechanism  which 
promptly  reduces  an  increase  or  decrease  in  the  amount  of  fluid 
contained  in  the  body  to  its  normal  limits. 

Pawlow  further  showed  on  dogs  that,  during  complete  rest  and 
sensory  inactivity,  blood  pressure  from  day  to  day  does  not  alter. 
On  the  other  hand,  it  increases  slightly  after  meals,  and  sinks 
slightly  in  the  morning.  It  regularly  becomes  lower  after  a  warm 
bath.  The  abrupt  upward  or  downward  changes  in  arterial 
pressure  are  due  to  disturbances  of  vascular  innervation  (infra, 
Chapter  X.). 

The  results  of  a  series  of  experiments  which  Colombo  carried 


256 


PHYSIOLOGY 


CHAP. 


out  in  Mosso's  laboratory  with  a  sphygmomanometer  applied  to 
the  fingers  of  a  healthy  man  are  only  partially  in  agreement  with 
Pawlow's. 

He  found  that  when  a  man  is  removed  from  all  external  and 
internal  influences  liable  to  produce  disturbance  of  the  vasomotor 
functions,  the  lateral  pressure  of  the  digital  arteries  fluctuates 
constantly  within  24  hours  between  a  minimum  of  65  and  a 
maximum  of  100  mm.  Hg  (average  80-85).  The  greatest  decrease 
occurs  after  meal  times,  the  greatest  rise  during  hours  most 
removed  from  meals.  The  daily  curve  of  blood  pressure  must 
accordingly  run  an  opposite  course  to  that  of  pulse  frequency  and 
temperature.  As  a  matter  of  fact  the  pulse  is  accelerated  when 
arterial  pressure  falls,  and  becomes  slower  when  it  rises,  which  is 
apparently  the  expression  of  some  compensatory  mechanism. 

The  depressor  effect  of  meals  is  certainly  due  to  active  vascular 
dilatation  of  the  digestive  organs,  and  possibly  to  the  entrance  of 
a  small  amount  of  peptones  into  the  circulation.  Colombo  found 
that  the  highest  fall  of  pressure  (which  may  amount  to  20.  mm.  Hg) 
is  apparent  two  hours  after  meals,  when  the  absorption  of  the 
products  of  digestion  is  beginning. 

The  introduction  of  a  large  quantity  of  milk,  contrary  to  what 
might  be  expected,  produces  a  rise  in  pressure,  in  consequence  of 
the  overloading  of  the  circulation,  which  cannot  apparently  be 
compensated  by  depression  of  the  vascular  tone. 

Alcohol,  chloroform,  opium,  warm  baths,  sleep,  lower  the  blood 
pressure ;  cold  baths  and  coffee  raise  it. 

Gymnastics  and  massage  of  the  limbs  and  back  produce  a  rise, 
massage  of  the  abdomen  a  fall,  in  blood  pressure,  probably  because 
they  influence  the  vascular  tone  in  a  different  degree  and  in 
different  proportions. 

The  pressure  in  the  veins,  in  consequence  of  their  ready 
distension,  is  less  subject  to  fluctuation  than  arterial  pressure. 
Theoretically  it  may  be  assumed  that  all  the  circumstances  that 
produce  a  rise  or  fall  in  arterial  pressure,  cause,  or  may  cause,  a 
change  in  venous  pressure  in  the  opposite  direction.  Venous 
pressure  is  specially  affected  by  : — 

(a}  Increment  or  decrement  in  amount  of  blood. 

(6)  Kespiratory  movements  (to  be  discussed  later). 

(c)  Position  of  the  body  (according  to  the  laws  of  hydrostatics). 

VI.  Observations  on  the  velocity  of  the  circulation  have 
been  made  in  two  opposite  directions.  On  the  one  hand,  it  has 
been  attempted  to  determine  the  mean  velocity  with  which  the 
blood  moves  in  any  given  artery ;  on  the  other,  to  establish  the 
form  of  the  pulsatory  changes  of  velocity. 

At  present  we  must  confine  ourselves  to  the  methods  employed 
for  ascertaining  the  first  point. 

By  mean  velocity  of  the  blood  in  an  artery  is  meant  the  length 


viii      BLOOD -STKE AM:   MOVEMENT  IN  VESSELS      257 


of  the  blood  column  that  traverses  the  section  of  the  said  artery 
in  the  time-unit,  usually  1".  It  can  easily  be  calculated  when  the 
sectional  area  of  the  artery  and  the  amount  of  blood  that  traverses 
it  in  the  time-unit  are  known. 

The  first  to  attempt  the  exact  determination  of  this  point  was 
Volkmann  (1846).  His  method  was  adopted  by  Ludwig  (1867) 
who  perfected  Volkmann's  haemodromo  meter.  His  instrument  (the 
Stromuhr)  permitted  the  repetition  on  the  same  animal,  for  an 
indefinite  number  of  times,  of  the  determination  of  the  mean 
velocity  of  the  circulation,  so  that  its  variations  with  changes  of 
experimental  conditions  can  be  investigated. 

Lud  wig's  Stromuhr  or  haemo- 
dromometer  (Fig.  99)  consists  of 
two  glass  receivers  of  equal 
capacity  (A,  B),  which  com- 
municate above  by  a  U-bend, 
in  the  centre  of  which  there  is 
a  tube  opening  to  the  exterior. 
By  means  of  this  aperture  the  - 
bulb  A  can  be  filled  with  oil, 
and  bulb  B  with  physiological 
saline,  after  which  the  aperture 
is  closed  by  a  stop-cock.  The 
cannula  a  (which  communicates 
with  the  bulb  A)  is  then  con- 
nected with  the  central  end  of 
the  artery,  and  the  cannula  b 
(which  communicates  with  the 
bulb  B)  with  its  distal  end.  As  Fl,..!M). 
soon  as  the  blood  reaches  the 
stromuhr,  it  penetrates  A  and 
drives  the  oil  into  B,  when  the 
salt  solution  contained  in  the 

latter  is  driven  into  the  peripheral  part  of  the  artery.  When  the 
blood  has  completely  filled  the  'bulb  A,  the  two  receivers  which 
are  reversible  upon  the  metal  plate  c  are  changed  by  a  rapid  half- 
turn,  so  that  A  is  now  in  connection  with  the  cannula  b,  and  B 
with  cannula  a.  The  bulb  containing  oil  is  now  again  filled  with 
blood,  and  the  oil  once  more  driven  into  the  bulb  A,  and  so  on. 
If  the  number  of  turns  in  a  given  time  are  counted,  then  with 
known  capacity  of  the  receivers  it  is  easy  to  calculate  the  total 
quantity  of  blood  flowing  in  that  time  through  the  artery,  from 
which  the  quantity  passing  per  second  can  be  calculated. 

Tigers  tedt  modified  Lud  wig's  Stromuhr  by  substituting  for  the 
two  receivers  a  single,  accurately  calibrated  glass  cylinder,  along 
which  runs  a  hollow  metal  ball.  The  pressure  of  the  blood  drives 
this  ball  from  one  end  of  the  cylinder  to  the  other  ;  so  soon  as 

VOL.  I  s 


wig's  haemodromometer  or  Mroinuhr. 
A,  B,  (Mass  bulbs  of  equal  capacity  ;  «,  1>,  can- 
nulae  to  be  connected  with  central  ami  periph- 
eral trunks  of  artery  ;  c,  metal  plate  fixed  on  a 
support,  on  which  the  air-tight  metal  disc  in 
which  the  two  receivers  end  can  rotate. 


258  PHYSIOLOGY 


CHAP, 


this  occurs,  the  cylinder  is  reversed  by  a  mechanism  resembling 
that  of  Ludwig's  Stromuhr,  and  the  ball  moves  in  the  opposite 
direction,  driving  the  blood  before  it. 

We  also  invented  a  haemodromometer,  which,  with  the  utmost 
simplicity  of  construction,  presents  the  advantage  of  being  able 
to  vary  the  capacity  of  the  two  receivers,  which  correspond  to  the 
bulbs  of  Ludwig's  apparatus,  by  employing  two  elastic  bags  in 
a  receiver  full  of  water.  The  first  two  editions  of  this  text-book 
gave  the  description  and  figure  omitted  here  in  favour  of  the  new 
model  constructed  by  Hiirthle,  which  has  the  further  advantage  of 
automatically  registering  its  movements. 

Hiirthle 's  haemodrompmeter  (as  shown  in  Fig.  100)  consists 
essentially  of  an  inverted  U-tube,  in  one  branch  of  which  there  is 
a  cylindrical  receiver  containing  a  piston,  which  is  easily  movable 
from  the  top  to  the  bottom  and  the  bottom  to  the  top.  The  blood- 
stream, which  issues  from  the  central  end  of  the  artery  (carotid  in 
the  dog),  ascends  by  a  branch  of  the  said  tube,  penetrates  the 
cylindrical  receiver,  and,  by  lowering  the  piston,  empties  out  the 
fluid  (artificial  serum  with  which  it  was  filled  at  the  outset)  into 
the  distal  end  of  the  artery. 

When  the  ball  reaches  the  extreme  end  of  its  course,  the 
experimenter  at  once  reverses  the  blood  current  through  the 
cylinder  by  giving  a  half -turn  to  a  disc  beneath  it  by  means  of  a 
screw.  The  blood  current  will  then  flow  into  the  cylinder  from 
below,  driving  the  piston  up,  and  turning  the  blood  into  the  distal 
end  of  the  artery. 

The  reversal  of  the  current  is  repeated  each  time  the  ball 
reaches  the  top  or  bottom.  The  interval  between  one  reversal  and 
the  other  expresses  the  duration  of  each  filling  and  emptying  of 
the  cylinder  that  measures  the  current.  The  excursions  upward 
and  downward  of  the  ball  are  transmitted  by  a  system  of  pulleys 
to  a  lever  writing  on  the  smoked  paper  of  a  rotating  drum.  A 
Deprez  signal  simultaneously  records  the  time  on  the  same  drum, 
while  an  elastic  manometer  (Hiirthle)  applied  to  the  artery  shows 
,the  pulsatory  oscillations  of  the  arterial  pressure. 

The  tracings  in  Fig.  101  are  reproduced  from  those  obtained 
by  Hiirthle  with  his  ingenious  haemodromometer  (reduced  by  one- 
third),  which  serves  at  the  same  time  for  a  spring  manometer 
recording  the  oscillatory  pulsations  in  pressure  and  for  an  electric 
time-marker. 

These  haemodromometric  methods  are  certainly  not  free  from 
defects,  and  they  give,  not  the  normal  absolute  values  of  current 
velocity  in  any  given  artery,  but  values  as  much  lower  than  the 
normal  as  the  resistances  artificially  opposed  to  the  passage  of  the 
blood  through  the  measuring  apparatus  are  greater.  Since,  how- 
ever, these  new  resistances  are  a  fixed  and  constant  coefficient, 
they  do  not  interfere  with  the  value  of  the  comparative  results. 


vin      BLOOD -STEEAM:   MOVEMENT  IN  VESSELS      259 
On  the  other  hand,  the  method  still  occasionally  adopted  after 


FIG.  100.— Hiirthle's  recording  haemodrompmeter,  partly  schematic,  partly  in  section,  a,  b,  Can- 
nula«  connecting  with  central  and  peripheral  ends  of  artery  ;  c,  well-calibrated  glass  cylinder 
into  which  the  blood  flows,  pushing  the  piston  now  from  above  downward,  now  from  below 
upwards.  The  piston  is  connected  by  a  thread  passing  over  two  pulleys,  to  the  lever  d, 
which  records  on  a  rotating  drum  the  movements  of  the  piston,  i.e.  the  filling  or  emptying  of 
the  cylinder.  Below  the  metal  plate  which  supports  the  measuring  cylinder  is  a  movable 
disc  e,  with  handle,  /,  connected  with  the  metal  band  g,  which  turns  the  disc  180°,  reversing 
the  current  and  crossing  the  rubber  tubes  a'  b'.  Before  applying  the  apparatus,  the  whole  of 
the  tubing  a,  a',  b,  b',  c  is  filled  with  physiological  saline.  This  is  effected  by  the  tube  h  carry- 
ing a  tap,  which  is  shut  off  when  the  tubes  are  completely  filled. 

Harvey  (who  first  employed  it  to  measure  the  velocity  of  the 
circulation)  is  entirely  fallacious,  since  it  is  based  on  the  amount 


260 


PHYSIOLOGY 


CHAP. 


of  blood  which  escapes  in  the  unit  of  time  from  a  divided  artery. 
In  this  case  all  the  peripheral  resistances  which  the  blood  has  to 
overcome  under  physiological  conditions  are  artificially  excluded. 
Even  when  the  lumen  of  outflow  is  artificially  constricted  (e.g.  by 
introducing  a  glass  cannula  of  narrow  bore)  in  order  to  build  up  a 
resistance  similar  to  that  which  the  blood  normally  encounters,  it 
is  impossible  to  obtain  any  correct  values  of  current  velocity,  both 
because  we  do  not  know  if  the  resistance  added  is  of  the  same 
value  as  that  subtracted,  and  because  in  any  case  the  animal  is 
losing  the  Wood  that  flows  out,  which  sets  up  quite  abnormal 
conditions. 


Fio.  101. — Curve  of  velocity  and  pressure  of  blood  in  left  carotid  of  a  dog  of  13  kgrms.  (Hiirthle  and 
Tschuewsky.)  The  upper  tracing  is  divided  along  the  abscissa  into  six  periods  (Pi,  Pn,  etc.), 
at  which  the  current  in  the  measuring  cylinder  was  reversed.  The  spaces  comprised  between 
the  horizontal  lines  of  the  tracing  correspond  with  0  c.c.  of  blood.  The  curves  of  the  second 
level  represent  the  pulsatory  oscillations  of  blood  pressure  in  the  central  cannulae  of  the 
haemodromometer,  and  were  recorded  with  a  spring  manometer.  The  bottom  line  gives  the 
time  in  seconds.  The  vertical  line  C.d.c.  of  the  third  period  gives  the  moment  at  which  the 
right  carotid  was  compressed,  which  produced  an  augmentation  both  of  velocity  and  of  pressure 
in  the  left  carotid,  as  shown  in  the  tracing. 

The  experimental  results  obtained  by  Dogiel  and  Nicolaides 
with  Ludwig's  stromuhr  are  somewhat  meagre  owing,  no  doubt,  to 
the  very  variable  conditions  that  affect  the  velocity  of  current  in 
any  given  artery.  They  show  that  both  in  the  carotid  and  the 
femoral  of  the  dog  or  rabbit  the  velocity  may  alter  greatly  from 
one  moment  to  another.  Since  the  first  determinations  usually 
show  a  higher  value  than  the  subsequent,  it  was  conjectured  that 
this  was  due  to  a  commencement  of  clotting  at  the  insertion  point 
of  the  cannula.  This  supposition  was,  however,  excluded,  inasmuch 
as  the  same  fact  was  observed  with  blood  that  had  been  rendered 
incoagulable  by  peptone  injection,  viz.  that  velocity  diminished  as 
the  experiment  proceeded,  more  often  in  the  carotid,  less  frequently 
iii  the  crural  artery. 


vin      BLOOD-STREAM:   MOVEMENT  IN  VESSELS      261 


The  following   are  some   of  the   data    derived    from    Dogiel's 
researches  : — 


Animal. 

Duration  of  Observa- 
tion in  seconds. 

Velocity  in  mm.; 

Weight  of 
Animal 
in  kgrms. 

Rabbit  . 

110 

226-94 

17 

Dog       . 

80 

733-349 

23  '3 

» 

127 

520-243 

12-1 

63 

458-411 

3'2 

,,   (division    of    vago  -  sym- 

pathetic) 

45 

339-204 

3-6 

The -velocity  of  the  blood-flow,  which  is  essentially  a  function 
of  the  resistances  in  that  part  of  the  circulation  to  which  the 
haemodromometer  is  applied,  must  rise  and  fall  with  the  increase 
and  decrease  of  resistance.  It  is  probable  that  the  mere  manipu- 
lation necessary  for  inserting  the  cannula  in  the  artery  is  sufficient 
to  -produce  relaxation  of  it  and  its  principal  branches,  thereby 
determining  an  abormal  rise  of  current  velocity,  which  soon  falls 
again  in  consequence  of  the  recovery  of  normal  vascular  tone. 

Dogiel  further  showed  that  there  may  be  a  compensatory  rise 
in  current  velocity  in  the  carotid  on  exciting  the  splanchnic  nerve  ; 
this  has  no  direct  action  on  the  carotid  region,  but  since  it 
provokes  contraction  of  the  vessels  in  the  abdominal  viscera,  it 
increases  resistance  in  a  remote  vascular  region  of  considerable 
extent.  He  also  observed,  when  using  two  stromuhrs  on  the  same 
animal,  that  the  velocity  in  the  carotid  and  the  femoral  arteries 
may  vary  now  in  the  same,  now  in  the  opposite  sense.  This  shows 
the  great  adaptability  of  capacity  in  the  various  vascular  regions, 
the  mechanism,  of  which  will  be  studied  in  the  next  chapter. 

Tschuewsky  (1903),  using  Hurthle's  recording  stromuhr,  has 
made  a  great  many  observations  on  dogs,  upon  the  mean  velocity 
of  the  blood  in  the  different  arteries,  and  under  various  experimental 
conditions.  The  following  table  gives  the  average  of  his 
results : — 


Artery. 

Experimental  Conditions. 

Average 
Weight  of 

Average        Average  Blood 
Diameter  of  ,     Pressure  in 

Average 
Velocity  in 

kgrms. 

Vessel  in  mm.        mm.  Hg. 

mm.  per  sec. 

Crural    . 

Nerves  of  limb  intact 

137 

2-5                      77 

128 

>  > 

„        cut 

14-6 

2'8                    88 

275 

Carotid  . 

Vagus    and    sym- 

pathetic  intact 

14'1 

3-27                  92-6 

241/2 

Erom  this  table  it  appears  that  the  velocity  is  normally  much 
lower  in  the  crural  artery  than  in   the  carotid,    and  that  after 


262 


PHYSIOLOGY 


CHAP. 


division  of  the  nerves  to  the  limb  (paralytic  vaso-dilatation)  the 
diminution  of  resistance  due  to  relaxation  of  vascular  tone  may 
cause  current  velocity  to  rise  to  more  than  double  the  normal. 

Tetanic  excitation  of  the  nerve,  on  the  contrary,  increases 
resistance  by  increase  of  vascular  tone  (vaso-constriction)  and  com- 
pression of  the  vessels  by  muscular  contraction,  with  consequent 
diminution  of  velocity,  as  shown  in  the  following  table : — 


Experimental  Conditions. 

Weight  of 
Dog  in 

Diameter  of 
Crural 

Average  Pressure 
of  Blood  in  Crural 

Average  Velocity 
in  Crural  Artery, 

kgrms. 

Artery,  mm. 

Artery,  mm.  Hg. 

mm.  per  second. 

Before  excitation  . 

11-2 

2-45 

8-'3  -0 

201-7 

During    tetanisation    of 

sciatic      nerve      with 

strong  currents  . 

84-8 

96-6     . 

After-effect  of  excitation 

81-5 

236-5 

The  results  of  experiments  to  determine  the  effect  of  temporary 
anaemia  of  different  vascular  regions  due  to  compression  of  the 
arteries  are  also  interesting. 

The  following  are  examples : — 


Average  Duration 

Average  Pressure    Average  Velocity 

Experimental  Conditions. 

of  Compression 
in  seconds. 

of  Blood  in  caro- 
tid in  mm.  Hg. 

in  carotid  in  mm. 
per  second. 

I.  Before  compression 

109-2 

308-2 

During       compression      of 

carotid  of  opposite  side  . 

23-3 

114-2 

394-6 

II.  Before  compression 

120-1 

293-3 

After    temporary   compres- 

sion  of  arteries   on    the 

side  to  which  the  liaenio- 

dromometer     has      been 

applied   .... 

21-0 

127-0 

411-7 

From  this  table  we  see  (a)  the  marked  compensatory  rise  of 
velocity  on  constriction  of  an  adjacent  area  ;  (V)  the  marked  rise  of 
velocity  after  temporary  anaemia  of  the  vascular  area  on  the  same 
side,  owing  to  the  diminution  of  peripheral  resistance  due  to  the 
resulting  vaso-dilatation. 

As  regards  the  mean  velocity  of  the  blood-flow  in  the  veins,  we 
have  already  stated  that  it  must  be  less  than  that  in  the  corre- 
sponding arterial  region,  in  proportion  as  the  total  area  of  the 
venous  system  is  greater. 

The  velocity-  of  blood-flow  in  the  axes  of  the  capillaries  can  be 
determined  without  difficulty  under  the  microscope  by  measuring 
the  time  taken  by  a  red  corpuscle  to  traverse  a  certain  distance, 


vin      BLOOD-STREAM:   MOVEMENT  IN  VESSELS      263 

which  can  be  measured  by  an  ocular  micrometer.  The  values 
obtained  with  this  method  by  different  observers  are  shown  in  the 
following  table  by  Tigerstedt : — 


Animal. 

Velocity  in  mm.  sec. 

Observers. 

Frog,  abdominal  muscle 

0-28 

Hales 

Frog  larva,  tail    . 

0-57 

E.  H.  Weber 

Frog,  interdigital  membrane 

0-51 

Valentin 

55                               5  )                                      55 

0'2o 

Vorkmann 

Salamander  larva,  gill 

0-36 

Vierordt 

Frog  larva,  tail    . 

0-40 

A'olkmann 

Fish,  caudal  fin   . 

0-12 

Puppy,  mesentery 

0-80 

- 

The  velocity  of  the  red  corpuscles  in  the  capillaries  of  the  retina 
was  ingeniously  determined  by  Vierordt  upon  himself,  by  means 
of  their  entoptic  images.  If  we  look  without  accommodating  the 
eye  at  a  large  clear  surface,  e.g.  the  sky,  numerous  shining  points 
appear  which  move  one  after  the  other  by  tortuous  paths ;  these 
are  the  blood-corpuscles  seen  entoptically,  owing  perhaps  to  con- 
centration of  light  upon  their  concave  discs.  Vierordt  projected 
these  images  upon  a  surface  of  11-16  cm.  from  the  eye,  and  there 
determined  the  space  traversed  by  a  single  corpuscle  in  the  time- 
unit.  From  this  he  deduced  a  velocity  of  0'5-0*9  mm.  per  sec. 
The  values  of  the  velocity  of  blood-flow  in  the  capillaries  is  of 
special  interest,  owing  to  the  fact  that  it  is  possible  from  these  to 
deduce  the  approximate  extent  of  the  total  area  of  the  capillary 
system.  Since  the  velocity  of  the  blood  in  the  vascular  system  is 
inversely  proportional  to  its  total  area,  we  can  calculate  from  the 
area  of  the  aorta  and  the  velocity  of  the  blood  in  the  aorta  and  its 
capillaries  the  total  area  of  these  last,  inasmuch  as  the  area  of  the 
capillary  system 

_  area  of  aorta  x  velocity  in  aorta 
velocity  in  capillaries 

If  we  admit  the  value  of  0*5-1  m.  as  the  mean  velocity  in  the 
aorta  and  that  of  0-5-l  mm.  in  the  capillaries  per  second,  thus,  with 
an  aortic  area  of  44  cm.2,  we  obtain  the  value  of  8800-2200  cm.2  for 
the  total  area  of  the  capillary  system  (Tigerstedt) 

VII.  We  must  now  pass  on  to  the  methods  devised  in  order  to 
analyse  the  pulsatory  oscillations  of  blood  pressure,  of  current 
velocity,  and  of  the  volume  of  the  vessels.  All  three  phenomena 
are  intimately  related  among  themselves,  and  all  depend  on  the 
fact  that  the  flow  of  blood  from  the  heart  to  the  arteries  is  not 
continuous,  but  occurs  in  intermittent  waves,  which  coincide  with 
the  cardiac  systole.  We  will  begin  by  reviewing,  collectively,  the 

VOL.  I  s  a 


264  PHYSIOLOGY  CHAP. 

observations  made  on  these  three  phenomena  in  order  subsequently 
to  compare  the  results. 

The  so-called  sphygmographic  methods  have  yielded  perfect 
sphygmograms,  which  give  an  exact  graphic  representation  of  the 
pulsatile  oscillations  of  pressure. 

Even  the  ancient  physicians,  more  particularly  Herophilus, 
Erasistratus,  and  Galen,  recognised  by  touch  some  of  the  chief 
characteristics  of  the  arterial  pulse,  and  the  alterations  in  frequency 
(pulsus  frequens  et  rarus),  magnitude  (p.  magnus  et  parvus),  rate 
of  dilatation  (p.  celer  et  tardus),  hardness  or  compressibility 
(p.  durus  et  mollis),  regularity  or  irregularity  of  rhythm  (p.  inter- 
mittens,  altcrnans,  intercurrens),  and  lastly,  in  the  form  of  the  pulse 
wave  (p.  dicrotus  seu  bis  feriens).  But  all  these  and  many  other 
distinctions  of  pulse,  as  laid  down  by  Galen,  are  founded  far  too 

much  on  subjective 
appreciation.  Cusano 
(1565)  made  a  great 
advance  when '  he  first 
used  a  watch  to  count 
the  beats ;  still  greater 
progress  was  made  by 
Vierordt  (1855)  who 
first  demonstrated  the 
possibility  of  register- 
ing  the  pulse  auto- 
matically,  although  his 

Fi<;.   102. — Marey's  contrivance  for  transmitting  the  move-         ,  ,       ,Fj 

merits  of  the  spring  to  the  writing-lever  of  the  sphygmo-  SpiiygmOgraph    did    not 

graph,    m, Steel  spring;  >>,  button  compressing  the  artery,  aiin«apr|       \n       rrivinrr 

connected  above  with  a  little  rod,  of  which  the  screw  bites  8110066(1       in      giving      a 

into  the  wheel  of  the  axis  a,  which  moves  the  lever  I  from  f.riip       liiftlirp       of      thp 

above  downwards  in  the  direction  of  the  arrow.  ~  f"7  U 

form  ot  the  pulse-wave 
or  the  pulsatile  oscillations  of  arterial  pressure. 

The  first  sphygmograph  which  accurately  recorded  the  form  of 
the  pulse  was  that  constructed  by  Marey  in  1860,  which  found 
ready  acceptance  among  physicians  owing  to  the  elegance  of  the 
method,  and  the  exaggerated  hopes  of  clinical  advantage  that  were 
founded  on  it.  The  essential  part  of  Marey's  sphygmograph  was  a 
steel  spring,  pressed  against  the  radial  artery  by  a  button,  which 
transmitted  the  pulsations  to  a  long  and  very  light  lever,  by  which 
they  were  recorded  exactly,  in  a  magnified  form,  upon  a  metal 
plate  covered  with  smoked  paper,  propelled  at  a  uniform  rate  by 
clockwork.  Fig.  102  shows  the  mode  of  transmitting  the  move- 
ments of  the  spring  to  the  lever  according  to  the  most  recent 
improvements,  and  Fig  103  shows  the  complete  instrument  applied 
to  the  forearm.  The  sphygmograms  obtained  with  Marey's 
sphygmograph  may  vary  considerably  under  different  conditions  of 
health  and  disease;  but  all  have  one  characteristic  feature — a 
rapidly  ascending  and  slowly  descending  period  can  always  be 


viii      BLOOD -STEE AM:  MOVEMENT  IN  VESSELS      265 


distinguished.  The  former,  produced  by  the  pulse-wave  which 
starts  from  the  aorta,  usually  reaches  its  culminating  point 
without  interruption ;  the  latter,  on  the  contrary,  shows  several 


Fm.  103. — Marey's  direct  sphygmograph,  applied  to  the  radial  artery. 

oscillations,  one  of  which  (the  second,  expressed  in  a  rise  preceded 
by  a  slight  depression)  is  rarely  absent  in  pulse  tracings.  It  is 
known  as  the  dicrotic  wave,  and  con- 
sists in  a  negative  wave  (dicrotic 
notch),  immediately  followed  by  a 
secondary  positive  wave. 

It  has  been  proved  by  innumer- 
able control  experiments  of  Buissou, 
Marey,  Landois  and  others,  that  the 
sphygmograms  thus  obtained  do  really 
reproduce  the  form  of  the  pulsatile 
oscillations  of  blood  pressure,  and  that 
their  constant  dicrotisrn  is  no  factitious 
product  of  the  registering  apparatus. 
Here  we  need  only  say  that  sphygmo- 
grams obtained  with  the  sphygmoscope 
or  other  elastic  manometers  (Fig.  67, 
p.  205)  present  the  same  dicrotic  form. 
Moreover,  as  Landois  showed,  it  is 
possible  to  obtain  autosphygmograms, 
by  dividing  the  artery  of  an  animal, 
and  directing  the  rhythmical  jet  of 
blood  against  a  rotating  drum  covered 
with  filter -paper  (liaemautograpliy). 
As  shown  by  Fig.  104,  the  form  of  the 
haemautogram  agrees  perfectly  with 
those  from  the  sphygmograph  and  sphygmoscope :  while  the 
dicrotic  wave  is  even  more  apparent,  this  being  the  only  really 
important  feature  of  the  pulse  curve  that  we  need  consider. 

Since  the  dicrotic  wave  persists,  and  is  even  more  pronounced 
in  autosphygmograms,  it  is  proved  to  be  the  result  of  a  positive 


FIG.  104.— Auto-sphygmogram  (Haem- 
autogram)  from  posterior  tibial 
artery  of  large  dog.  (Landois.)  p, 
Primary  wave  ;  (/,  dicrotic  wave. 


266 


PHYSIOLOGY 


CHAP. 


wave  of  central  origin  and  centrifugal  course — which  excludes  the 
hypothesis  still  maintained  by  some,  that  it  arises  in  a  peripheral 
and  centripetally  reflected  wave.  This  last  hypothesis  is  also 
irreconcilable  with  the  fact  that  the  secondary  positive  wave  is 
nearly  always  preceded  by  a  negative  wave  which,  as  we  shall  see 
immediately,  can  only  be  of  central  origin. 


FJC 


105.  —  Sphygmograms  from  radial  artery  (,sV),  and  changes  produced  by  inhalation  of 
ainyl  nitrite  (SV).     (A.  1).  Waller.) 


The  long  experience  of  nearly  half  a  century,  during  which 
Marey's  sphygmograph  (or  other  sphygmographs  which  are  only 
modifications  of  this  instrument)  has  been  employed  clinically,  has 
proved  it  to  be  of  very  little  diagnostic  value.  We  have  for 
many  years  insisted  on  this  fact,  and  for  the  following  reasons. 


Fio.  106. — Marey's  transmission  Bphygraograph  applied  to  radial  artery.  This  only  differs  from 
the  direct  sphygmograph  in  that  the  movements  of  the  button  of  the  spring  are  not  trans- 
mitted by  a  lever,  but  by  a  receiving  tambour,  which  then  transmits  them  to  a  second 
tambour  writing  upon  the  revolving  drum  of  the  kymograph. 

It  is  quite  true  that  the  sphygmogram  is  the  true  expression 
of  the  form  and  magnitude  of  the  pulsatile  oscillations  in  pressure 
in  the  artery  to  which  the  instrument  is  attached,  but  it  is  far 
from  representing  their  absolute  values.  Local  arterial  pressure  is 
indeed  dependent  on  many  variable  factors ;  on  the  tension  of  the 
spring,  the  elasticity  and  tone  of  the  arterial  walls,  the  amount 
and  degree  of  torpor  in  the  surrounding  soft  parts.  From  all  these 
causes,  the  size  of  the  pulse,  i.e.  the  amplitude  of  the  sphygmogram, 
is  in  no  definite  ratio  either  with  the  volume  of  blood  driven 
from  the  heart  to  the  arteries  at  every  systole,  nor  with  the  height 


viii      BLOOD-STREAM:   MOVEMENT  IN  VESSELS      267 


of  pressure  within  the  artery  investigated ;  it  is  only  proportional 

to  the  magnitude  of  the 

local  oscillations  of   the 

pulse,  which  (as  we  saw 

on    p.    248)   are,    ceteris 

paribus,  in  inverse  ratio 

to  the  tension  of  the  ar- 
terial walls.    As  a  matter 

Of  fact,  not  only  the  prim- 
ary, but  also  the  secondary 

dicrotic   wave    is    lower 

with  greater,  and  higher 

with      reduced     arterial 

pressure.     Not  even  this 

fact,    however,    can     be 

taken  as  a  general  law, 

since  the  varying  degree 

of  contraction  or  relaxa- 
tion in  the  artery  explored 

has  great  influence  upon 

the    amplitude    of     the 

sphygmic      undulations. 

In  order  to  realise  this, 

we  have  only  to  consider  the  marked  changes  that  appear  in 
the  form  and  magnitude  of  the  sphygmo- 
gram  after  inhalation  of  amyl  nitrite,  which 
immediately  produces  depression  of  arterial 
tone  (Fig.  105).  The  beats  of  the  heart 
become  more  frequent,  and  yet  the  amplitude 
of  the  primary  as  well  as  of  the  dicrotic 
wave  increases. 

Far  more  interesting  and  instructive,  from 
the  clinical  point  of  view,  is  the  comparison 
of  the  sphygniogram  with  the  simultaneously 
recorded  cardiogram,  as  also  the  comparison 
of  two  or  more  sphygmograms  simultaneously 
recorded   from  different  arteries.     For  this 
purpose,  however,  the  direct  sphygmograph 
IDS.— Bdgren's  sphygmo-  is  not  suitable,  and  others  with  air  transmis- 
af  receivTg^iSuht-  sion  musfc  beresorted  to.  These  are  essentially 
tached  to  a"  semicircular  identical  with  cardiographs,  but  are  different 

«™ng  intended  to  tit  round     ./.  •  ,,  •    j!       j    j    j? 

neck.    The  pressure  of  in  form,  sin ce .they  are  intended  for  use  on 


FIG.  107.— Burdon-Sanderson's  cardiograph,  which  can  also 
be  used  as  a  sphygmograph  for  the  carotid,  and  a 
pneumograph  (Zimmermann's  type).  The  apparatus  rests 
on  three  ebonite  feet,  which  can  be  adjusted  by  screws. 
It  is  fixed  by  a  band  to  the  thorax  or  neck,  so  that  the 
central  button,  which  has  a  steel  spring  (the  tension  of 
which  can  be  altered  by  a  screw),  presses  against  the 
spot  at  which  the  beat  of  the  heart  or  carotid  pulse  is 
most  perceptible.  The  transmission  by  air  of  the  move- 
ments of  the  spring  is  effected  through  a  receiving 
tambour,  the  position  of  which  in  regard  to  the  spring 
can  be  regulated  by  a  screw. 


the  exploring  button  upon 
the  artery  is  regulated  by  a 
plate  applied  to  the  neck, 
which  stretches  the  spring 


the  several  arteries.     One  of  these  trans- 
mission sphygmographs   is  that   of   Marey 


more  or  less  according  to  the  (represented   in    Fig.    106),  for   the   radial 
artery.     A  simpler  model  is  that  of  Edgren 
for  the  same  artery.     Burdon- Sanderson's  cardiograph  (Fig.  107) 


268 


PHYSIOLOGY 


CHAP. 


can  be  used  for  the  carotid,  femoral,  or  other  arteries,  as  also 
Edgren's  sphygmograph,  or  any  kind  of  tympanum  with  an 
elastic  membrane  kept  stretched  by  a  spiral  spring,  and  provided 
with  an  exploring  button  in  the  centre,  which  can  be  pressed 
against  the  artery  to  be  examined  (Fig.  108). 

VIII.  The  comparison  of  cardiograms  and  sphygmograms 
simultaneously  recorded  on  the  same  revolving  cylinder  gives  all 
the  data  necessary  to  establish  the  chief  characteristics  of  the  two 
tracings.  Those  of  Fig.  109  were  obtained  by  Edgren  on  a  healthy 
youth  of  twenty-five.  The  various  features  of  the  cardiographic 
curve  (a,  b,  c,  d,  e,f,  g,  h,  i)  are  indicated  by  vertical  lines.  Since 


FIG.  100.—  Cardiograms  (C)  and  sphygmoscrams  (S)  of  carotid  of  a  healthy  subject  of  -2u.    (Edgren.) 
a,  b,  c,  d,  e,  /of  the  cardiograms  correspond  with  the  «],  foj,  cj,  </1;  e\,f\  of  the  sphygmograms. 

these  are  obvious,  they  need  no  further  description.  After  what 
was  said  in  the  previous  chapter  (Fig.  80,  p.  224)  we  know  that  the 
point  a  corresponds  with  the  onset  of  systole,  when  the  first  sound 
of  the  heart  begins  to  be  heard,  and  the  point  /  with  the  onset  of 
diastole,  when  the  semilunar  valves,  which  have  already  been 
closed  at  the  systolic  dead  point,  are  thrown  into  tension,  and  the 
second  sound  develops.  In  the  sphygmographic  curve  of  the 
carotid  the  point  coinciding  with  a  shows  no  marked  feature. 
The  primary  sphygmic  wave  which  starts  from  the  arterial  orifice 
first  reaches  the  carotid  at  the  point  V  The  interval  ab',  therefore, 
represents  the  time  taken  up  by  the  transmission  of  the  pulse 
wave  from  the  arterial  orifice  to  the  carotid,  plus  the  time  of  the 
latent  systole,  i.e.  that  between  the  commencement  of  the  con- 
traction of  the  myocardium  and  the  moment  of  the  opening  of  the 


viii      BLOOD-STEEAM:   MOVEMENT  IN  VESSELS      269 

semilunar  valves  (point  I  of  the  cartographic  curve).  Since 
the  points  &,  c,  d,  e,  f  of  the  cardiogram  correspond  to  the  same 
number  of  points  on  the  sphygmogram  at  V,  c,  d',  e',f,  but  all 
with  a  delay,  equal  approximately  to  the  interval  aa',  it  follows 
that  this  interval  expresses  the  time  occupied  by  the  transmission 
of  the  primary  wave  from  the  arterial  orifice  to  the  carotid,  and 
that  the  intervals  ab,  a'bf  represent  the  time  of  latent  systole. 

The  interval  &c,  which  can  hardly  be  seen  on  the  cardiogram 
as  a  slight  drop  in  the  curve,  corresponds  to  the  interval  Vc' 
marked  by  the  sharply  ascending  curve  of  the  primary  wave. 
The  interval  cd,  indicated  by  a  slight  rise  of  the  cardiographic 
line,  corresponds  to  the  interval  c'd',  indicated  on  the  sphygmogram 
by  a  tract  that  is  almost  horizontal  (the  plateau}.  The  interval 
de,  corresponding  to  d'e',  both  on  the  cardiogram  and  on  the 
sphygmogram  shows  a  slowly  descending  line :  and  the  intervals 
ef  and  e'f  correspond  in  both  curves  with  rapidly  descending  lines. 

Leaving  aside  the  features  c  and  d  which  are  less  conspicuous, 
and  have  only  a  dubious  significance,  it  is  evident,  or  at  any  rate 
extremely  probable,  that  the  entire  interval  be  represents  the 
period  of  systolic  outflow  or  evacuation,  during  which  the  heart, 
in  consequence  of  the  diminution  in  its  volume,  exerts  a  constantly 
decreasing  pressure  on  the  intercostal  space  to  which  the  cardio- 
graph is  applied.  In  the  sphygmographic  curve  these  periods  are 
represented  by  the  interval  Vc'  in  which  the  primary  pulse  wave 
is  traversing  the  artery. 

The  small  interval  ef  coincides  with  the  beginning  of  active 
diastole,  during  which,  owing  to  the  diminished  tension  of  the 
cardiac  muscle,  the  intercostal  space  on  which  the  button  of  the 
cardiograph  rests,  sinks  in.  This  corresponds  to  the  lines  e'f  of 
the  sphygmogram,  which  represent  a  true  negative  wave  that  pre- 
cedes the  secondary  or  dicrotic  wave. 

To  understand  the  origin  of  this  dicrotic  wave  it  is  enough 
to  consider  that  at  the  commencement  of  diastole  an  enormous 
difference  between  aortic  and  intraventricular  pressure  arises  :  this 
causes  the  blood  column  to  gravitate  towards  the  semilunar  valves 
which  are  already  closed,  throwing  them  into  vibration  so  that 
they  develop  the  second  sound,  and  set  up  the  negative  wave  in 
the  artery,  owing  to  their  distension  towards  the  conus  arteriosus. 
The  sharp  tension  of  the  valves  is  succeeded  by  their  elastic 
reaction,  which  produces  the  positive  dicrotic  wave  that  follows 
immediately  on  the  negative  wave.  The  great  majority  of  physi- 
ologists, including  Grashey,  Edgren,  Hoorweg,  Hiirthle,  are 
unanimous  in  accepting  this  explanation  of  the  dicrotic  wave.  To 
us  its  central  origin  appears  conclusive,  on  account  of  the  negative 
wave  that  precedes  it  and  can  only  be  caused  by  the  rapid 
recession  of  the  column  of  blood  in  the  aortic  bulb,  which 
•distends  the  valves  and  pushes  them  down  towards  the  conus 


270 


PHYSIOLOGY 


CHAP. 


arteriosus  ; — not  by  the  reflux  of  a  certain  amount  of  blood  from 
artery  to  ventricle,  to  produce  closure  of  the  valves,  as  is  arbitrarily 
assumed  by  Edgren. 

The  points  g,  h,  i,  which  are  distinguishable  on  the  long 
descending  shoulder  of  the  cardiographic  curve,  of  course  find  no 
analogue  in  the  sphygmogram,  because  after  closure  of  the  semi- 


Fio.  110. — Comparison  of  synchronous  sphygmograms  of  carotid  (Nc)  and  of  radial  (.s'r).     (Edgren.) 

lunar  valves  changes  of  pressure  within  the  ventricle  can  no  longer 
be  transmitted  to  the  arteries.  Here  we  will  only  say  that  the 
point  g,  which  marks  the  lowest  depression  of  the  cardiographic 
curve,  very  probably  corresponds  with  the  moment  at  which  the 
negative  pressure  in  the  ventricle  exerts  the  maximum  of  aspira- 


Sf 


Fio.  111. — Synchronous  sphygmograms  of  carotid  (.Sic)  and  femoral  (Sf).    (Edgren.) 

tion ;  that  the  point  h  marks  the  moment  at  which  active  diastole 
ceases,  and  passive  diastole  or  the  true  rest  of  the  heart  begins; 
and  that  finally  the  point  i  (which  is  usually,  but  not  constantly, 
visible  in  cardiographic  tracings)  points  to  the  moment  at  which 
presystole  commences,  causing  a  certain  degree  of  passive  dilatation 
of  the  ventricle,  as  perceived  in  a  gentle  rise  of  the  cardiograph 
button. 

When  the  rate  at  which  the  cylinder  rotates  is  known,  and  the 


viii      BLOOD-STEEAM:   MOVEMENT  IN  VESSELS      271 

characteristics  of  the  cardiographic  and  sphygmographic  curves,  as 
described  above,  are  well  marked,  the  length  in  millimetres,  and 
corresponding  period  in  fractions  of  a  section,  of  the  chief  phases 
of  the  cardiac  cycle  in  man  can  easily  be  determined.  It  is  well 
to  make  these  determinations  from  tracings  obtained  from  one 
healthy  individual,  with  constant  experimental  conditions  during 
the  research.  The  data  thus  obtained  are  of  approximately  absolute 
value  for  the  individual  under  observation,  and  are  certainly  far 
more  trustworthy  than  the  average  data  derived  from  comparison 
of  results  yielded  by  various  individuals  under  varying  experimental 
conditions. 

From   the  careful   measurements    taken    by    Edgreu    upon    a 


Sr 


FIG.  112.  —Synchronous  sphygrnograms  of  radial  (X?-)  and  femoral  (X/).    (Edgren.) 

healthy  man  of  25,  whose  pulse  beat  70  times  per  minute,  the 
following  values  were  obtained,  which  may  be  taken  as  the  average 
of  ten  successive  cardiac  revolutions  :  — 

Period  of  tension  ... 
Period  of  efflux  .... 
Total  duration  of  systole 


-  ab-   4'OV  n 
=  be  =  11-71 

nn.  =  0-U934  sect 
,     =0-2342 

=  tie  =16-38 

,     -0-3276 

=  «/  =   2-60 
=  fa  =  24-14 

,     -0-0520 
,     -  0-4828 

=  ea  =  26-74 

,     -0-5348 

=  ««-43-12 

,     =0-8624 

Total  duration  of  diastole    . 

Total  duration  of  cardiac  revolution 


IX.  If  the  pulse  of  the  carotid  and  radial,  or  the  carotid  and 
the  femoral,  or  the  femoral  and  radial  are  registered  simultaneously 
as  shown  in  Figs.  110,  111,  112,  it  is  possible  to  determine  with 
great  accuracy  the  time  occupied  in  the  propagation  of  the  primary 
wave  V,  or  the  dicrotic  wave  /',  by  deducing  it  from  the  delay 
between  the  appearance  of  the  two  waves  in  the  arteries  most 
remote  from  the  heart.  This  delay  is  represented  in  the  three 
figures  by  the  intervals  W  and  f'f.  If  they  are  measured  with 
a  millimetre  scale,  it  will  be  seen  that  their  length  alters  with  the 
difference  between  the  two  arteries  of  which  the  sphygmograms  are 
compared.  It  will  also  be  seen  that  the  wave  b'  appears  simultane- 
ously in  the  femoral  and  the  radial,  while  the  wave  f  appears  with 
a  measurable  delay  in  the  femoral. 

Edgren  obtained  the  following  results  as  the  average  of  a 
number  of  measurements  of  these  intervals  in  sphygmograms  taken 


PHYSIOLOGY 


CHAP. 


on  two  healthy  individuals  25  years  of  age.  The  delay  between 
the  radial  pulse  and  the  carotid  for  the  wave  V  —  3*93  mm.  =  0*0786 
seconds,  for  the  wave/' =  3*96  mm.  =  0*0792  seconds. 

Since  the  distance  from  the  semilunar  valves  to  the  point  on 
the  carotid  at  which  the  sphygmograph  was  applied  was  20  cm. 
and  to  the  corresponding  point  on  the  radial  80  cm.,  the  time 
difference  found  corresponded  to  a  length  of  60  cm.  From  these 
data  the  time  of  transmission  of  the  wave  ~b'  from  heart  to  carotid 
can  l>e  calculated : 

3-93  :  r  =  60  :  20  ;  x  -  1'31  mm.  =0-0262  seconds  ; 
<ind  from  heart  to  radial : 

3-93  +  1-31  =  5-24  mm.  =  0'1048  seconds. 

By  a  similar  calculation  the  propagation  of  the  wave  f  from 
heart  to  carotid  is  found  to  be : 

3-96  :  .r  =  60  :  20  ;  x=  1-32  mm.  =  0-0264  seconds  ; 
and  from  heart  to  radial : 

3-96 +  1-32  =  5-28  mm.  =  0-1056  seconds. 

Repeating  the  same  measurements  and  calculations  for  the 
single  series  of  tracings  obtained  on  the  two  young  men,  Edgren 
obtained  the  results  appended  on  the  following  table  :— 


Distance. 


From  heart  to  carotid  I. 

I 
From  heart  to  radial  I. 

II- 

From  heart  to  femoral  I 


Time  of  Transmission 

of  Primary  Wave  V. 

of  Uicrotic  Wave  J  '. 

d  I. 

1-31  mm.     0-0262  sec 

| 
1-32  mm.     0-0264  sec. 

II.       . 

1-36 

0-0272 

1-36 

0-0272    , 

I. 

5-24 

0-1048 

5-28 

0-1056    , 

II. 

6-32 

0-1064 

5-32 

0-1064    , 

•al  I.     . 

5-50 

0-1100 

1     6-35 

0-1270    , 

II.     . 

5'31 

0-1062 

6-32 

0-1264    , 

From  these  data  Edgren  found  it  easy  to  calculate  the  rate  of 
transmission  of  the  two  waves,  i.e.  the  distance  they  traversed  in 
•one  second  (the  unit  of  time). 

The  results  are  given  in  the  following  table  :— 


Velocity  of  Transmission 


Distance. 

of  Primary  Wave. 

of  Dicrotic  Wave. 

From 

carotid  to  radial 

=  60  cm. 

7-63  m. 

7'53  m. 

58   „. 

7-32  ,, 

7-32  ,, 

From 

carotid  to  femoral 

=  52    „  .         . 

6'20  „ 

5-20  „ 

» 

52    „   . 

6-59  „ 

5-40  „ 

•• 

vin       BLOOD-STREAM:   MOVEMENT  IN  VESSELS       273 

These  results  agree  well  with  those  of  previous  authors,  notably 
with  those  of  Keyt.  The  differences  depend  principally  on  the 
respective  degree  of  elasticity  of  the  arteries  explored,  and  the 
respective  height  of  the  mean  blood  pressure  within  them  ;  the 
greater  the  elasticity  of  the  arteries,  the  higher  the  blood  pressure, 
and  the  greater  will  be  the  velocity  of  wave  transmission  (Moens, 
Grunmach,  Keyt). 

Edgren's  results,  like  the  earlier  conclusions  of  Keyt,  lead  us 
to  think  that  the  velocity  of  the  wave  in  the  vessels  is  higher  in 
the  upper  limbs  than  in  the  lower.  Edgren  further  found  by 
comparing  the  velocity  of  the  primary  and  the  dicrotic  wave  that 
it  is  less  in  the  latter.  The  difference,  which  can  hardly  be 
detected  betwreen  heart  and  radial  artery,  is  conspicuous  between 
the  heart  and  the  femoral  artery,  as  appears  from  the  above  tables. 

The  wave-length  can  easily  be  calculated  from  the  velocity  of 
transmission  of  the  waves  and  from  their  number,  since  it  is  in 
direct  proportion  to  the  rate  of  propagation  (h)  and  inversely 
proportional  to  the  number  of  vibrations  (ri),  according  to  the 

equation    A  -  -.     If  with  Edgren  we  reckon  the  time  of  systolic 

outflow  =  0'23  seconds,  the  number  of  vibrations  in  one  second  will 
be  equal  to  5*75,  and  their  velocity  of  propagation  (taking  the 
average  of  that  calculated  by  Edgren  for  the  primary  wave)  is 
equal  to  6-93  m.  per  second.  Accordingly  the  wave-length 

6'93 

l'20  m.     Since  in  an  adult  the  distance  from  heart  to 


small  arteries  of  the  foot  is  a  little  greater,  these  arterial  tracts  of 
the  body  are  the  only  ones  long  enough  to  accommodate  the  entire 
length  of  the  pulse  wave,  and  the  end  of  the  wave  usually  passes 
the  orifice  of  the  aorta  when  the  front  of  it  has  already  reached 
the  peripheral  arteries  (Tigerstedt),  so  that  these  pulsate  during 
the  whole  of  the  systolic  outflow. 

We  know  experimentally  how  many  influences  react  on  the 
pulse-rate  ;  e.g.  the  lowering  of  blood  pressure  and  dilatation  of  the 
vessels  produced  by  heat,  by  amyl  nitrite,  and  by  profound  narcosis. 
The  pulse  is  perceptibly  slowed,  as  can  be  measured  not  merely  in 
artificial  narcosis  on  animals,  but  also  in  physiological  sleep,  and 
on  man.  Patrizi  compared  the  velocity  of  the  pulse  wave  in  the 
waking  state  and  in  deep  sleep,  by  means  of  experiments  on  a  boy 
of  13,  as  also  the  pulsations  of  the  brain  (the  boy  had  lost  part  of 
the  bony  substance  of  his  cranium)  and  of  the  feet. 

Velocity  of  propagation  in  waking  state,  6-50  in.  per  second. 
Velocity  of  propagation  in  sleep,  5-77  in.  per  second. 

X.  The  pulsatile  oscillations  of  pressure  in  the  sphygmograms 
must  be  distinguished  from  the  pulsatile  oscillations  of  velocity, 
which  are  also  determined  by  the  rhythmical  undulations  of  the 

VOL.  I  T 


274 


PHYSIOLOGY 


CHAP. 


heart.  Vierordt  (1858)  was  the  first  to  construct  an  apparatus 
for  the  study  of  these  oscillations.  Vierordt's  haemotachometer  is 
based  on  the  principle  of  the  hydrostatic  pendulum,  used  by 


FIG.  113. — Chauveau's  haemodrometer.     Left-hand  figure  shows  the^instrument  as  a  whole  ; 
right-hand,  a  vertical  section  of  it.     (Explanation  in  text.) 

engineers  to  measure  the  rate  of  a  stream  of  water.  His  method 
was  perfected  and  developed  by  Chauveau  (1860),  who  constructed 
a  very  ingenious  recording  apparatus  on  the  same  principle,  which 
he  termed  a  haemodromograph. 

Fig.  113  shows  this  apparatus  as  a  whole  on  the  left,  and  in 


vm       BLOOD-STREAM:   MOVEMENT  IN  VESSELS       275 

section  on  the  right.  The  tube  TT  is  intended  for  insertion  in 
the  carotid  artery  of  a  horse  or  other  large  animal ;  L  represents 
the  bar  of  the  pendulum  which  ends  in  a  very  light  plate  or  disc 
p,  dipping  into  the  axis  of  the  blood-stream.  The  bar  of  the 
pendulum  passes  at  m  through  a  rubber  membrane,  which  acts 
as  a  pivot  to  the  pendulum,  and  is  then  prolonged  externally  till 
it  joins  a  Marey's  air  tympanum.  The  tube  TT  has  a  narrow 
longitudinal  cleft  along  which  the  terminal  disc  of  the  pendulum 
•can  move,  in  accordance  with  the  oscillations  of  current  velocity  ; 
these  are  reversed  at  the  membrane  of  the  receiving  tambour, 
which  again  transmits  them  to  a  tambour  with  a  writing  lever. 
No  blood  can  enter  the  groove  in  which  the  bar  of  the  pendulum 
oscillates  freely,  because  it  is  connected  with  an  external  space 
filled  with  an  alkaline  solution  through  the  side  tube  B,  and  then 
closed  with  a  clamp.  The  sphygmoscope  S  is  applied  at  the  side 
of  the  tube  TT,  and  records  the  oscillations  of  pressure  on  a 
revolving  cylinder  by  means  of  a  second  writing  tambour  which 
acts  synchronously  with  the  first. 

Just  as  sphygmograins  do  not  give  absolute  values  of  oscilla- 
tions of  blood  pressure,  so  the  tachygrams  or  dromogranis  recorded 
by  Chauveau's  haeniodromograph  yield  only  relative  values  of  the 
oscillations  of  current  velocity  above  and  below  the  zero  line, 
which  is  reached  when  there  is  no  movement,  because  the  disc  of 
the  pendulum  is  under  equal  pressure  on  both  sides.  In  order  to 
ascertain  the  absolute  value  of  velocity  and  its  oscillations,  the 
apparatus  must  be  graduated.  Chauveau  did  this  by  sending  a 
stream  of  water  through  it,  of  which  the  outflow  was  regulated 
until  the  deflections  of  the  pendulum  attained  the  maximal, 
minimal,  and  mean  values  obtained  on  applying  the  apparatus  to 
the  carotid  of  the  horse.  It  is  then  easy  to  determine  the  velocity 
corresponding  to  these  points,  by  calculating  it  from  the  diameter 
of  the  arteries,  and  from  the  respective  amount  of  outflow,  obtained 
with  different  degrees  of  deflections  of  the  pendulum. 

Chauveau  and  his  pupils  Bertolus  and  Leroyenne  were  able  to 
determine  that  the  velocity  of  the  blood-flow  amounted  to  520  mm. 
per  second  in  the  carotid  of  the  horse  during  systole,  to  220  mm. 
during  the  dicrotic  wave,  and  to  150  mm.  during  diastole. 

When  the  carotid  is  ligatured  on  one  side,  a  compensatory  rise 
of  velocity  is  visible  in  the  other  carotid.  During  the  masticating 
movements  also,  in  consequence  of  a  dilatation  of  the  vessels  of 
the  masticatory  muscles  and  salivary  glands,  there  is  an  increase  of 
circulatory  velocity  in  the  carotid,  which  may  become  five  or  six 
times  greater  than  the  initial  value.  When  any  considerable 
vascular  dilatation  is  produced  by  dividing  the  spinal  cord,  the 
rate  of  flow  is  considerably  augmented  during  systole,  but  becomes 
extremely  low  during  diastole.  At  the  end  of  diastole  the 
velocity  is  greater  in  the  peripheral  than  in  the  central  arteries ; 


276  PHYSIOLOGY  CHAP. 

at  the  commencement  of  systole,  on  the  other  hand,  it  increases 
more  in  the  central  than  in  the  peripheral  arteries. 

It  is  no  less  interesting  to  examine  the  features  presented  by 
tachygrains  as  compared  with  sphygmograms  simultaneously 
recorded.  Fig.  1 14  gives  an  instructive  example  of  these  tracings 
as  obtained  by  Lortet,  another  of  Chauveau's  pupils.  Point  1 
corresponds  to  the  moment  in  which  the  primary  systolic  wave,  on 
reaching  the  carotid,  produces  a  simultaneous  rise  in  pressure 
and  in  velocity.  At  point  2  the  pressure  reaches  its  maximum 
when  the  velocity  has  already  begun  to  fall,  in  accordance  with  the 
increase  of  elastic  tension  in  the  distended  artery,  by  which  the 
velocity  of  the  movement  of  the  blood  is  proportionately  moderated 


FIG.  114. — Tachygram  (V)  and  sphygmogram  (P)  registered  simultaneously  on  carotid  artery  of 
horse,  with  Chauveau's  haemodroinogiaph.    (Lortet.) 

and  depressed.  Point  3  probably  corresponds  to  the  moment  at 
which  the  systolic  efflux  ceases  and  the  closure  of  the  semilunar 
valves  ensues,  and  point  4  to  the  moment  at  which  the  latter  are 
thrown  into  tension  owing  to  the  beginning  of  diastole,  which 
makes  the  blood  column  gravitate  and  recede  against  the  already 
closed  semilunar  valves,  and  in  the  sphygmogram  determines 
the  negative  wave  that  precedes  the  positive  dicrotic  wave.  This 
interpretation  is  in  fact  confirmed  by  the  course  of  the  tachy- 
graphic  curve,  which  at  points  3  and  4  drops  below  the  zero  line 
indicating  a  backward  movement  of  the  current,  followed  rapidly 
by  the  dicrotic  rise.  In  the  entire  interval  from  4  to  1  (which 
corresponds  approximately  to  the  periods  of  peri-  and  pre-systole), 
the  pressure  curve  shows  a  slowly  falling  line,  which  expresses  the 
decrease  of  arterial  pressure  in  proportion  as  the  elastic  reaction 
of  the  artery  drives  the  blood  into  the  capillaries  and  veins. 
Velocity  also  decreases  at  the  same  time,  but  more  slowly. 

XL  During  the  passage  of  the  pulse  wave  through  the  arteries, 


vm       BLOOD-STKEAM :   MOVEMENT  IN  VESSELS       277 

it  produces  a  transverse  dilatation  and  elongation,  which  are  in 
relation  with  the  pulsatile  oscillations  of  pressure.  The  lengthening 
of  the  arteries  produces  a  movement  of  the  vessels  at  each  wave 
of  blood  that  traverses  them,  as  is  clearly  visible  in  arteries 
ligatured  after  amputation.  Normally,  however,  since  the  arteries 
are  not  free  to  elongate  in  the  longitudinal  direction,  they  become 
laterally  curved  when  rectilinear,  and  increase  their  curvature  if 
(as  in  old  people)  they  have  a  winding  course ;  and  when  (as  in 
the  aortic  and  pulmonary  area)  they  form  a  free  arch  with  a  short 
radius  of  curvature,  the  curvature  tends  at  each  systolic  wave  to 
change,  and  to  assume  a  longer  radius,  by  a  mechanism  similar  to 
that  of  the  metallic  manometer  of  Bourdon. 

The  elongation  of  the  arteries,  since  it  is  plainly  visible,  was 
known  to  the  older  surgeons ;  the  transverse  dilatation  on  the 
other  hand  is  a  less  obvious  phenomenon,  so  that  in  the  eighteenth 
century  some  of  the  clinicians  (De  la  Mure  in  particular)  denied 
it  altogether,  and  held  that  the  arterial  pulse  perceptible  to  touch 
is  the  effect  of  simple  vascular  locomotion.  Spallanzani  (1773) 
was  the  first  to  demonstrate  the  pulsatile  dilatation  of  the  aorta 
in  the  salamander  by  an  ingenious  experiment.  "  The  aorta  "  (he 
wrote)  "  pulsates  in  its  entire  length,  and  in  pulsating  it  dilates, 
but  not  equally  in  all  its  parts.  Where  it  arches,  its  diameter  is 
increased  by  a  third,  but  elsewhere  it  increases  only  about  a 
twentieth.  Although  my  eye  informed  jne  that  in  the  pulsations 
the  increase  in  diameter  or  bulging  of  the  aorta  occurred  more  or 
less  at  each  point  of  the  circumference,  I  employed  the  following 
method  to  illustrate  it : — I  passed  the  aorta  through  a  small  open 
metal  ring  which,  when  closed,  was  of  slightly  larger  diameter  than 
the  aorta.  When  the  aorta  dilated  in  its  pulsations,  the  empty 
space  between  it  and  the  ring  became  smaller ;  when  it  was  con- 
stricted the  space  became  larger.  I  then  diminished  the  capacity 
of  the  ring.  Now,  where  the  aorta  bulged,  that  is  where  there 
was  the  greatest  dilatation,  the  circular  space  was  lost  during  the 
cardiac  systole,  being  filled  in  every  direction  by  the  dilated 
vessel :  this  proved  decisively  that  the  aorta  in  pulsating  dilated  at 
all  points  of  its  circumference  "  (Dei  fenomeni  della  circolazione, 
Dissertazione  terza). 

In  proof  of  the  same  phenomenon,  Poiseuille  (1828)  introduced 
a  length  of  a  large  artery  into  a  long  chamber,  having  at  both 
ends  a  circular  hole  of  the  same  diameter  as  the  artery  it  was 
to  receive.  The  cover  of  the  chamber  (which  could  be  closed  so 
as  to  become  water-tight)  was  pierced  by  a  vertical  glass  tube 
provided  with  a  millimetre  scale.  After  the  chamber  containing 
the  artery  had  been  filled  with  fluid,  the  fluid  could  be  seen  to  rise 
in  the  tube  at  each  systolic  wave,  and  to  fall  at  each  diastole. 
Poiseuille  measured  the  increase  in  arterial  diameter  by  the  highest 
point  of  the  rise. 


278 


PHYSIOLOGY 


CHAP. 


This  experiment  of  Poiseuille  was  the  starting-point  for  the 
construction  of  the  apparatus  known  as  the  plethysmograph, 
because  it  serves  to  register  the  content,  i.e.  the  variations  in 
volume,  of  any  organ,  owing  to  the  dilatation  and  constriction  of 
the  vessels  it  contains.  It  is  easy  to  see  that  where  the  different 
organs  or  parts  of  the  body  are  highly  vascular,  the  total 
movements  of  passive  or  active  dilatation  or  constriction  of  all 
the  arterial  branches  they  contain  must  produce  very  consider- 
able variations  in  volume. 

In  order  to  estimate  these  variations  in  volume,  Piegu  (1846) 

introduced  a  limb  into  a  vessel 
filled  with  lukewarm  water  and 
closed  completely,  save  at  a 
point  through  which  passed  the 
vertical  tube  intended  to  show 
the  changes  in  volume.  He 
described  the  changes  in  volume 
depending  on  cardiac,  as  well  as 
those  depending  on  respiratory 
rhythm.  Chelius  (1850),  who 
was  not  acquainted  with  the 
previous  investigations  of  Piegu, 
investigated  the  changes  in 
volume  of  a  limb  by  the  same 
method,  and  with  the  same 
results. 

Ch.  Buisson  (1862),  who  dis- 
covered the  graphic  method  by 
means  of  air  transmission  to  a 
writing  tambour,  subsequently 
perfected  by  Marey,  was  the  first 
who  applied  it  to  the  plethysmo- 

for  recording  rapid  changes  of   volume  of    OTapllS  of  PiegU  and  ChellUS. 
the  hand,  which  are  transmitted  to  a  tarn-    c         A     -.-,•    -,    /.,  o/»r»\        -i.i_  Ar- 
bour with  highly  sensitive  lever.  A.  Fick  (1868),  with  the  same 

object,  connected  the  water-tight 

chamber  in  which  the  forearm  was  enclosed  with  a  recording 
water  manometer,  which  directly  recorded  the  pulsatile  changes  in 
volume  of  the  investigated  limb  upon  a  revolving  cylinder. 

A.  Mosso  (1874-75)  described  another  ingenious  plethysmograph, 
with  which  he  intended  to  record  in  absolute  values  the  changes 
of  volume  in  an  isolated  organ  or  a  limb.  Owing,  however,  to 
the  sluggishness  with  which  the  recording  apparatus  functions, 
it  is  incapable  of  following  the  rapid  passive  changes  due  to  the 
cardiac  rhythm,  while  it  is  able  to  record  the  slow  changes  in 
volume  due  to  the  active  contraction  and  dilatation  of  the  vessels, 
which  are  entirely  independent  of  cardiac  rhythm.  We  shall 
return  to  this  in  Chapter  X. 


Fia.  115. — Francois  -Franck's  plethysmograph, 


A' 


viii       BLOOD-STKEAM :   MOVEMENT  IN  VESSELS       279 

Frangois-Franck  (1876)  made  some  useful  modifications  in.  the 
details  of  Buisson's  apparatus,  giving  the  apparatus  the  form  of 
Fig.  115.  The  flask  placed  in  front  of  the  rubber  tube,  which 
joins  the  plethysmograph  with  the  writing  tambour,  cuts  out  the 
oscillations  of  the  fluid  along  the  vertical  tube.  The  method  and 
instrument  afterwards  used  by  Mosso  (1880)  for  recording  the 


FIG.  116. — A',  Plethysmogram  of  forearm  in  fasting  state.;  A,  the  same,  in  same  individual,  after 

a  meal.     (Mosso.) 

pulsatile  changes  in  the  volume  of  the  forearm,  to  which  he  gave 
the  name  of  hydrosphygrnograph,  is  very  similar. 

Among  the  various  results  of  more  or  less  importance  obtained 
by  the  plethysmographic  method,  we  can  here  only  refer  to  the 
form  of  the  curves  depending  on  the  pulsatile  oscillations  in 
volume  of  the  part  explored,  i.e.  to  vascular  plethysuiograms  and 
their  interpretation. 


FIG.  117.— V,  Plethysmogram  of  hand  taken  with  apparatus  of  Fig.  115,  the  oscillations  of  th" 
column  of  fluid  being  suppressed  by  the  bulb  interposed  between  the  exploring  apparatus  and 
the  recording  tambour.  (Fr.-Franck.) 

Vascular  plethysuiograms  are  very  similar  to  sphygmograms, 
and  exhibit  the  same  principal  features,  including  dicrotism,  as 
shown  in  Figs.  116  and  117.  Still  they  cannot  be  identical  since, 
as  we  have  seen,  sphygmograms  are  obtained  with  an  apparatus 
which  by  means  of  a  tense  spring  exerts  pressure  on  the  artery 
investigated,  depressing  its  lumen  to  a  greater  or  less  extent;  while 
plethysuiograms,  on  the  contrary,  depend  solely  on  the  alterations 
in  volume  of  the  forearm  or  hand,  all  external  pressure  being  as 
far  as  possible  excluded.  Since  the  flow  of  blood  in  the  veins  is 
continuous  and  uniform,  it  is  clear  that  the  changes  of  volume  in 


280 


PHYSIOLOGY 


CHAP. 


the  limb  can  only  depend  on  variations  in  the  blood-stream,  or  the 
velocity  with  which  the  blood  flows  into  the  arteries  at  different 
moments  of  the  cardiac  cycle.  It  is  possible  from  the  different 
inclinations  of  plethysmographic  curves  to  the  axis  of  the  abscissa 
to  construct  the  velocity  curve  (as  Tick  did),  and  thus  to  derive 
the  tachygram  from  the  plethysmogram. 

To  illustrate  this  conversion  of  volume  ciirve  into  velocity 
curve,  we  enlarged  the  first  plethysmogram  of  Fig.  117  by  means 
of  a  projection  apparatus,  subsequently  reducing  the  ordinates  by 
half.  This  gave  the  curve  represented  by  the  fine  line  in  Fig.  118; 
which  has  the  same  form  as  the  plethysmogram  of  Fig.  117  would 


FIG.  118.— The  tine  curve  is  the  first  plethysmogram  of  Fig.  117  enlarged  and  drawn  out. 
The  black  curve  is  the  tachygram,  constructed  graphically  by, measuring  the  degree  of  inclina- 
tion of  the  different  sections  of  the  plethysmogram.  (Luciani.) 

have  assumed  had  it  been  recorded  on  a  drum  rotating  at  double 
speed.  From  the  plethysmogram  thus  transformed  we  have 
graphically  constructed  the  tachygram  represented  by  the  black 
line  of  Fig.  118,  which  has  a  very  similar  course  to  that  of  the 
tachygram  recorded  by  Chauveau  and  Lortet  with  the  haemo- 
drornograph  (Fig.  114).  It  must  be  noted,  however,  that  the 
tachygram  thus  derived  from  the  plethysmogram  does  not  give 
absolute  values  of  oscillations  in  velocity,  and  that  the  abscissa  oo 
corresponds  not  to  zero  velocity  but  to  the  moments  in  which  the 
volume  of  the  forearm  was  unvaried,  because  the  arterial  inflow  at 
that  moment  balanced  the  venous  outflow. 

In  order  graphically  to  transform  plethysmograms  into  tachygrams,  the 
ordinates  of  which  represent  the  inclination  of  the  different  sections  of  the 
first  curve,  the  following  method  must  be  adopted.  At  any  point  P  of  the 
plethysmogram  draw  the  tangent  to  the  curve  ;  measure  the  trigonometric 


viii       BLOOD-STKEAM :   MOVEMENT  IN  VESSELS       281 


tangent  of  the  angle  which  this  makes  with  the  positive  direction  of  the 
axis  of  the  abscissa,  and  then  erect  upon  the  point  of  the  axis  of  the  abscissa 
corresponding  to  P  an  ordinate  proportional  to  the  measured  trigonometric 
tangent  Fick  has  given  a  very  practical  method  of  determining  these 
tangents. 

XII.  Having  thus  analysed  the  principal  phenomena  relating 
to  circulatory  pressure  and  velocity,  it  is  necessary  to  consider  a 
scheme  for  combining  them  synthetically.  With  this  object  Fig. 
119  shows  in  a  single  diagram  the  most  important  facts  of  the 
circulation  in  the  arteries,  veins,  and  capillaries.  In  the  arteries 


Artery. 


Capillary. 


Vein. 


FIG.  119.— Synthetic  diagram  of  progressive  variations  in  area  of  blood  current,  pressure,  and 
velocity,  in  the  three  main  sections  of  the  systemic  circulation.  (Gad  and  Fredericq.)  The 
schema  does  not  show  the  respiratory  and  vasomotor  oscillations  of  pressure  and  velocity. 

the  circulatory  area  (represented  by  the  total  section  of  the  vessels) 
increases  slowly  at  first  from  the  aorta  to  the  small  arteries,  and 
then  rapidly  from  the  small  arteries  to  the  capillaries.  Both  the 
pressure  and  the  velocity  curves  exhibit  the  same  general  course. 
The  pulse  and  the  cardiac  oscillations  of  velocity  in  the  arteries 
diminish  slowly  from  the  aorta  to  the  capillary  threshold. 

In  the  capillaries,  where  the  circulatory  area  becomes 
maximal,  pressure  continues  to  diminish  slowly,  and  velocity 
becomes  minimal  and  constant. 

In  the  veins  the  area  again  decreases,  rapidly  at  first,  then 
more  slowly  to  the  mouth  of  the  venae  cavae,  where,  however,  it 
is  more  extensive  than  at  the  aortic  orifice ;  pressure  decreases 
constantly,  becoming  negative  in  the  intrathoracic  veins ;  velocity, 
on  the  other  hand,  increases  more  slowly  from  the  farthest 


282  PHYSIOLOGY  CHAP. 

capillaries  to  the  venae  cavae,  where,  however,  it  is  lower  than  in 
the  aorta.  The  intra-  and  extra- thoracic  veins  nearest  the  heart 
show  gentle  pulsatile  oscillations,  either  of  pressure  or  velocity, 
which  coincide  with  the  presystole  and  systole  of  the  right  heart. 

If  we  consider  the  great  velocity  with  which  the  wave  move- 
ments, produced  by  the  intermittent  outflow  of  blood  from  the 
heart,  are  propagated  through  the  arteries,  it  is  evident  that  they 
have  no  connection  with  the  mean  velocity  of  the  circulation,  i.e. 
with  the  time  required  by  a  drop  of  blood  or  a  corpuscle  to 
traverse  the  whole  vascular  circuit  and  return  to  its  starting-point. 
"  Unda  non  est  materia  progrediens,sed  forma  materiae  progrediens." 
In  this  expressive  sentence  E.  H.  Weber  does  not  deny  that  the 
passage  of  the  sphygmic  wave  through  the  arteries  is  accompanied 
by  an  acceleration  of  the  flow,  and  is  thus  an  adjunct  to  the 
circulatory  movements ;  he  only  intended  to  make  a  sharp  dis- 
tinction between  the  average  velocity  with  which  the  blood  streams 
through  the  vessels  and  the  rate  of  transmission  of  the  pulse  wave, 
which  is  essentially  a  form  propagated  in  a  fluid. 

In  order  to  measure  (at  least  approximately)  the  duration  of 
the  entire  circulation,  E.  Hering  (1829)  invented  a  method  which 
consisted  in  the  injection  of  a  harmless  and  easily  recognisable 
substance  into  the  jugular  vein  of  an  animal,  after  which  a  sample 
of  blood  was  taken  from  the  jugular  vein  on  the  opposite  side  at 
intervals  of  five  seconds  (as  marked  by  a  metronome),  and  tested 
for  the  injected  substance.  He  selected  ferrocyanide  of  potash, 
since  its  presence,  even  in  minimal  quantities,  can  be  detected  by 
an  iron  salt,  in  the  presence  of  which  Prussian  blue  is  formed. 
The  results  which  he  obtained  on  the  horse  were  confirmed  at  a 
later  time  by  Vierordt  (1858),  and  applied  to  other  animals,  by  a 
method  which  was  a  little  more  exact  in  regard  to  measuring  the 
intervals  between  the  extraction  of  the  different  samples  of  blood. 

It  was  found  from  the  best  of  Bering's  experiments  on  horses 
that  the  blood  required  26*2  sees,  (on  an  average  of  nineteen 
experiments)  to  pass  through  the  entire  circulation  from  one 
jugular  vein  to  the  other.  This  path  from  one  jugular  to  the 
other  is  one  of  the  shortest  that  a  drop  of  blood  can  take,  in  order 
to  return  to  its  starting-point  after  traversing  the  entire  system. 
If,  on  the  other  hand,  the  ferrocyanide  is  injected  into  a  crural 
vein,  and  the  blood  from  the  crural  vein  on  the  other  side  tested,  the 
path  is  considerably  longer,  and  more  time  is  required.  Vierordt 's 
work  shows,  however,  that  the  time  difference  between  these  two 
paths  is  very  small,  so  that  the  blood  in  the  larger  arterial  and 
venous  vessels  circulates  very  rapidly,  any  marked  delay  first 
occurring  in  the  capillaries  and  the  smallest  vessels. 

The  discovery  that  the  average  time  of  circulation  varies 
among  the  different  mammals,  and  that  it  is  shorter  in  small  than 
in  larger  animals,  is  certainly  among  the  most  important  results  of 


vin       BLOOD-STKEAM :   MOVEMENT  IN  VESSELS       283 

Vierordt's  many  observations.  When,  further,  we  compare  the 
time  of  circulation  with  the  number  of  heart-beats  required  to 
complete  it,  we  arrive,  according  to  Vierordt's  experimental  data, 
at  the  fact  that  twenty-six  to  twenty-nine  pulsations  are  necessary 
in  every  animal,  independent  of  the  mass  of  its  body,  to  drive  the 
blood  through  the  whole  circulation  from  one  jugular  to  the  other. 
This  is  seen  from  the  following  table : — 


Animal. 

Time  of  Circulation 
in  seconds. 

i  Pulse  Frequency 
per  minute. 

Number  of  Pulsations 
in  One  Circulation. 

Rabbit    .... 

7-46 

220 

26-1 

Goat       .         .         . 

14-14 

110 

26-0 

Dog        .... 

167 

96 

267 

Horse  (Hering) 

31-5 

55 

j 

28-8 

As  regards  the  time  of  the  circulation  in  man,  Vierordt  thinks 
it  probably  stands  midway  between  that  of  the  dog  and  the  horse, 
i.e.  he  estimates  it  =  27'1  sees.,  which  with  a  pulse-frequency  of  72 
per  minute  corresponds  to  27'7  heart-beats. 

These  data  for  the  circulation  time  obtained  by  the  methods  of 
Hering  and  Vierordt  express  not  the  mean  velocity  with  which 
the  blood  circulates  in  the  vessels,  but  rather  the  maximal 
velocity,  i.e.  that  of  the  axial  lines  of  the  fluid  flowing  through  the 
vessels  (see  p.  189).  V.  Kries  (1887)  accordingly  proposed  to 
reduce  Vierordt's  figures  by  half,  to  obtain  the  value  of  the  average 
velocity  of  the  circulation.  By  the  laws  of  hydrodynamics,  the 
mean  velocity  of  a  fluid  traversing  a  tube  must  be  equal  to  half 
the  greatest  velocity  of  the  axial  current.  Tigerstedt,  however, 
pointed  out  that  the  theory  of  the  passage  of  fluids  was  only 
applicable  to  the  capillaries  on  the  assumption  that  the  stream  of 
fluid  is  free  from  solid  particles,  which  depress  the  value  of  the 
maximal  velocity  in  the  axial  current.  We  know  that  the 
erythrocytes  which  move  in  the  axial  current  are  so  large  that 
they  almost  fill  the  capillary  lumen,  hence  the  mean  velocity 
in  the  blood  capillaries  must  certainly  be  somewhat  more  than 
half  the  maximal  velocity.  Still  it  can  be  positively  affirmed  that 
the  average  time  of  circulation  must  be  less  than  that  given  by 
Bering's  method. 

BIBLIOGRAPHY 

In  addition  to  Bibliography  at  the  end  of  Chap.  VII.  (p.  231)  see  :— 
E.  H.  u.  W.   WEBER.     Wellenlehre  auf  Versuche  gegriindet.     Leipzig,  1825.— 

Observationes    anat.    et    phys.      Lipsiae,    1825. — Ber.    d.    sachs.    Gesell.    d. 

Wissenschaften,  1850.— Arch.  f.  Anat.  und  Physiol.,  1851-1853. 
VOLKMANN.     Die  Hamodynamik.     Leipzig,  1850. 
BONDERS.     Physiologic  des  Menschen.     Leipzig,  1859. 
A.  FICK.     Medicinische  Physik.     2nd  ed.     Braunschweig,  1866. 
LANDOIS.     Lehre  vom  Arterienpuls.     Berlin,  1872. 


284  PHYSIOLOGY  CHAP,  vm 

MA  KEY.     Traveaux  du  lab.     Paris,  1875-1878. 

MOENS.     Die  Pulscurve.     Leiden,  1878. 

A.  Mosso.     Ricerche  sfigmografiche,  R.  Accad.  delle  scienze  di  Torino,  1878.     R. 

Accad.  dei  Lincei,  1887. 

GRASHEY.     Die  Wellenbewegung  elastischer  Rbhren.     Leipzig,  1881. 
A.  FICK.     Die  Druckcurve  und  die  Geschwindigkeitscurve  in  der  A.  radialis  des 

Menschen.     Wurzburg,  1886. 

VON  KRIES.     Studien  zur  Pulslehre.     Freiburg,  1891. 
A.  Mosso.     Sphygmomanometre  pour  mesurer  la  pression  du  sang  chez  1'homme. 

Arch.  itah.de  biologie,  1895. 
HURTHLE.       tjber   eine  Methode  zur   Registrierung  des  arteriellen  Blutdrucks 

beim   Menschen.      Deutsche  med.   Wochenschr.,   1896.     Beschreibung  einer 

registrierenden  Stromuhr.     Pfliigers  Arch.,  xcvii.,  1903. 

RiVA-Rocci.     Un  Nuovo  Sfigmomanometro.     Gazzetta  niedica  di  Torino,  1896-97. 
M.  L.  PATRIZI.     II  Progredire  dell'  onda  sfigmica  nel  sonno  fisiologico.    Arch.  ital. 

de  biol.,  xxxvii.,  1897. 
DUCCESCHI.     Un  Nuovo  Metodo  di  sfigmografia.     Arch,  di   fisiol.  del  Fano,   i., 

1904. 
TSOHUEWSKY.     Uber  Druck,  Geschwindigkeit  und  Widerstand  in  der  Strombahn 

der  Art.  carotis  ecc.     Pfliigers  Arch.,  xcvii.,  1907. 

Recent  English  Literature  : — 
.1.   H.  M'CuRDY.     The  Effect  of  Maximum  Muscular  Work  on  Blood  Pressure, 

Amer.  Journ.  of  Physiol.,  1901,  v.  95. 
L.  HILL.     On  the  Residual  Pressures  in  the  Vascular  System  when  the  Circulation 

is  arrested.     Journ.  of  Physiol.,  1902,  xxviii.  122. 
R.  BURTON-OPITZ.     Muscular  Contraction  and  the  Venous   Blood -Flow.     Amer. 

Journ.  of  Physiol.,  1903,  ix.  161. 

R.  BURTON-OPITZ.     Venous  Pressure.     Amer.  Journ.  of  Physiol.,  1903,  ix.  198. 
0.  H.  BROWN  and  C.  C.  GUTHRIE.     The  Effects  of  Intravenous  Injections  of  Bone- 
Marrow  Extracts  upon  Blood  Pressure.     Amer.  Journ.  of  Physiol.,  1905,  xiv. 

328. 
P.  M.  DAWSON.     The   Lateral    "Blood   Pressures"    at   Different   Points   of  the 

Arterial  Tree.     Amer.  Journ.  of  Physiol.,  1905-6,  xv.  244. 
T.    LEWIS.     The    Influence  of  the    Venae   Comites  on  the  Pulse  Tracing,  with 

special    reference    to    Valsalva's    Experiment    and    Dicrotism  ;    a    note    on 

Anacrotism.     Journ.  of  Physiol.,  1906,  xxxiv.  391. 
T.  LEWIS.     The  Factors  influencing  the  Prominence  of  the  Dicrotic  Wave.     Journ. 

of  Physiol.,  1906,  xxxiv.  414. 
0.    RIDDLE  and   S.    A.    MATTEWS.      The  Blood    Pressures  of  Birds   and   their 

Modification  by  Drugs.     Amer.  Journ.  of  Physiol.,  1907.  xix.  108. 
T.  LEWIS.     Studies  of  the  Relationship  between  Respiration  and  Blood  Pressure. 

P.  i.  and  ii.     Journ.  of  Physiol.,  1908,  xxxvii.  213,  233. 
E.  C.  SCHNEIDER  and  C.  A.  HEDBLOM.     Blood  Pressure,  with  special  reference  to 

High  Altitudes.     Amer.  Journ.  of  Physiol.,  1908,  xxiii.    90. 


CHAPTER    IX 

PHYSIOLOGY   OF    CARDIAC    MUSCLE    AND    NERVES 

CONTENTS. — -1.  Intrinsic  processes  by  which  cardiac  rhythm  is  determined  and 
regulated.  2.  Extrinsic  chemical  conditions  of  cardiac  activity.  3.  Effects  ot 
ligation  and  section  on  different  parts  of  the  heart.  4.  Automatic  or  reflex 
activity  of  heart.  5.  Myogenic  or  neurogenic  origin  of  cardiac  rhythm.  6. 
Evidence  for  these  conflicting  theories.  7.  Special  mode  in  which  cardiac  muscle 
reacts  to  external  stimuli.  8.  Regulation  of  cardiac  rhythm  by  nervous  system  : 
inhibitory  or  diastolic  nerves.  9.  Accelerator  or  systolic  nerves.  10.  Theory  of 
anabolic  action  of  diastolic  nerves  and  katabolic  action  of  systolic  nerves.  11. 
Afferent  nerves  of  heart  or  other  parts  of  the  body  which  influence  cardiac  rhythm. 
12.  Nerve-centres  for  cardiac  nerves  ;  their  tonic  excitability,  and  theory  of 
regulation  of  cardiac  rhythm.  Bibliography. 

THE  mechanical  functions  of  the  heart  and  vessels,  as  discussed  in 
the  last  two  chapters,  are  modified  by  a  variety  of  oscillations  or 
changes.  Between  certain  limits  these  changes  not  only  come 
within  the  scope  of  normal  vital  activity,  but  also  satisfy  the 
physiological  necessity  for  adapting  both  the  general  velocity  of 
circulation,  and  the  distribution  of  blood  in  the  several  parts  of  the 
body,  to  the  different  external  conditions  and  temporary  needs  of 
the  whole  organism,  or  of  its  several  organs  or  tissues. 

The  physiological  changes  in  the  activity  of  the  heart  consist 
in  increased  or  diminished  frequency  or  force  of  its  beats ;  the 
physiological  changes  in  the  activity  of  the  vessels  consist  in  their 
dilatation  or  constriction  (particularly  in  the  small  arteries),  as 
determined  by  the  expansion  or  contraction  of  the  muscle  cells  of 
which  they  are  constructed. 

Even  to  the  lay  mind,  it  is  obvious  that  these  modifications 
and  adaptations  of  the  activity  of  the  heart  and  vessels  depend 
essentially  on  the  nervous  system,  which  is  the  supreme  regulator 
of  all  important  vital  functions.  From  the  fact  that  the  heart 
responds  to  the  psychical  emotions  by  various  modifications  of  its 
activity,  sprang  the  old  Aristotelian  belief  that  it  is  the  seat  of  the 
soul — a  belief  still  surviving  in  popular  ideas  and  expressions.  The 
fact  that  the  emotions  readily  produce  blushing  and  pallor  of  the 
countenance  shows  that  the  nervous  system  is  capable,  independent 
of  the  circulatory  centre,  of  modifying  the  blood  supply  to  the 
several  vascular  regions. 

285 


286 


PHYSIOLOGY 


CHAP. 


With  the  object  of  determining  the  limits  of  this  regulatory 
activity  of  the  nervous  system  as  exactly  as  possible,  we  shall  in 
the  next  two  chapters  discuss  the  better  ascertained  and  more 
important  facts  of  human  physiology,  with  respect  to  the  physio- 
logical conditions  that  underlie  the  activity  of  the  heart  and 
vessels. 

I.  As  shown  in  Chapter  VII.,  the  mechanical  activity  of  the 
heart  is  due  to  the  regular  sequence  of  three  different  states  in  its 
muscles — contraction,  expansion,  and  rest.  In  order  to  obtain  a 
clear  idea  of  the  origin,  succession,  and  propagation  of  these  three 
states  in  the  different  segments  of  cardiac  muscle,  we  must  return 

to  this  subject  and 
attentively  study 
the  exposed  heart  of 
the  living  frog  or 
tortoise  (Fig.  120). 

On  cutting  the 
fraenuni,  which  at- 
taches the  posterior 
wall  of  the  ventricle 
to  the  dorsal  surface 
of  the  pericardium, 
and  lifting  up  the 
heart,  we  see  that 
the  contraction  com- 
mences along  the 
venae  cavae,  and 
spreads  from  these 

H •      \^    y  R '    \v  ''  ^  /  to  tne  smus  venosus 

in  which  they  unite. 
From  the  sinus 
venosus,  which  opens 
into  the  right 
cle,  th< 

ventricular  groove  ;  P,  P',  pulmonary  veins  ;  M,  L,  left  and  right    spreads     tO    the    tWO 
superior  vena  cava  ;  JV,  inferior  vena  cava  ;  R.  coronary  vein.          *     .    , 

auricles ;  from  the 
two  auricles  it  passes  to  the  ventricle;  and  from  the  ventricle, 
lastly,  to  the  bulbus  arteriosus,  which  contracts  actively  in  the 
frog,  as  first  noted  by  Spallanzani.  The  contraction  or  systole  of 
the  heart  thus  takes  the  form  of  a  wave,  which  originates  in  the 
afferent  vessels  and  passes  to  the  heart,  where  it  spreads  peristaltic- 
ally  from  auricles  to  ventricle,  leaving  the  heart  by  the  efferent 
vessels. 

It  should,  however,  be  noted  as  a  fact  of  great  importance  that 
the  peristaltic  wave  of  contraction  does  not  proceed  uniformly,  but 
undergoes  a  delay  or  block  at  the  junction  between  the  sinus  and 
the  auricles,  the  auricles  and  the  ventricle,  and,  lastly,  at  that 


FIG.  120.— 1  and  2,  Anterior  and  posterior  aspects  of  frog's  heart. 
At,  Auricles  ;  V,  ventricle  ;  A,  A,  rarai  of  aorta  ;  Ba,  aortic  bulb  ; 
Sv,  sinus  venosus;  Vci,  vena  cava  inferior;  Fes,  vena  cava 
superior;  Vp,  pulmonary  vein;  Vh,  hepatic  vein.  3  and  It, 
Anterior  and  posterior  aspects  of  tortoise  heart.  A,  A',  Pulmon- 
ary  arteries;  B,  B',  left  and  right  aorta;  D,  D',  left  and  right 
subclavian  arteries ;  H,  hemi-animlus  of  bulb ;  /,  auriculo- 


ix  CARDIAC  MUSCLE  AND  NERVES  287 

between  the  ventricle  and  the  bulbus  arteriosus.  It  therefore 
follows  that  when  the  auricles  begin  to  contract,  the  sinus  begins 
to  expand;  when  the  ventricle  enters  systole,  the  auricles  are 
commencing  diastole ;  when,  lastly,  the  systole  of  the  bulbus 
arteriosus  begins,  the  ventricle  is  entering  diastole.  The  two 
active  phases  (systole  and  diastole)  are  followed  by  the  state  of 
rest  or  functional  pause,  which  in  the  same  way  appears  earlier 
in  the  sinus  than  in  the  auricles,  and  in  the  auricles  than  in  the 
ventricle,  with  the  resting  phase  of  which  the  cardiac  cycle  or 
revolution  is  complete. 

These  phenomena,  which  are  easily  detected  on  the  frog  or  the 
tortoise,  are  in  complete  agreement  with  those  which  can  be  observed 
under  greater  difficulties  in  warm-blooded  animals.  In  these, 
too  (as  we  have  seen),  the  wave  of  contraction  arises  in  the 
large  veins,  which,  as  they  have  no  sinus  venosus,  open  directly 
into  the  auricle :  from  the  auricles  it  is  propagated  peristaltically 
to  the  ventricles,  where  it  is  arrested,  since  these  have  no  contrac- 
tile bulbi  arteriosi.  In  warm-blooded  animals,  too,  the  wave  of 
contraction  encounters  a  block,  or  momentary  delay,  at  the  passage 
from  auricles  to  ventricles,  so  that  the  diastole  of  the  auricles 
coincides  with  the  commencement  of  ventricular  systole,  a  neces- 
sary condition  for  the  perfect  functioning  of  the  cardiac  pump. 

From  these  fundamental  phenomena  arise  all  the  complex 
problems  relating  to  the  physiological  conditions  of  the  cardiac 
functions.  On  what  does  the  rhythmical  \action  of  the  heart 
depend  ?  What  are  the  external  chemical  conditions  indispensable 
to  its  activity  ?  Is  its  rhythm  of  a  reflex  nature,  dependent  on 
extrinsic  conditions  or  stimuli,  or  is  it  automatic  in  character, 
dependent  on  intrinsic  conditions  or  stimuli  within  the  heart  ? 
Is  it  a  function  of  the  nervous  system,  or  simply  a  property  per- 
taining to  the  cells  of  cardiac  muscle  ?  Is  the  peristaltic  contraction 
wave  propagated  by  way  of  the  nerves  or  by  the  muscle  cells  ? 
Why  does  the  wave  of  contraction  arise  in  the  venous  paths  that 
lead  to  the  heart ;  and  on  what  do  the  blocks  or  brief  delays,  to 
which  it  is  subjected  on  passing  from  one  segment  of  the  heart  to 
the  other,  and  which  are  of  such  great  importance  to  its  mechanical 
functions,  depend  ?  These  are  the  fundamental  problems  which 
have  to  be  examined. 


METHODS  OF  STUDYING  CARDIAC  MOVEMENT 

Cardiac  movement  must  be  studied  either  on  the  exposed  heart  in  situ,  or  on 
the  fully  isolated  heart.  The  frog's  heart  isolated  from  the  body  is  capable, 
provided  it  be  protected  from  drying  in  a  moist  chamber,  of  continuing  its 
normal  activity  for>  some  time  (several  days),  and  thus  represents  the  most 
accessible  object  for  the  study  of  cardiac  movements.  For  this  reason  the 
methods  employed  in  the  graphic  registration  of  these  movements  were 
especially  contrived  for  the  frog's  heart.  Observations  of  the  surviving  heart 


288 


PHYSIOLOGY 


CHAP. 


of  warm-blooded  animals  are,   on   the   contrary,  impossible,   except   under 

certain  special  conditions,  and  acquaintance  with  these  conditions  is  one  of 

the  most  recent  acquisitions  of  scientific  technique. 

A.  Cold-Blooded  Animals. — In  order  to  obtain  graphic  tracings  of  the 

cardiac   movements   in   the   frog  or  any  other   cold-blooded  animal,  three 

different  methods  may  be  em- 
ployed. Of  these  there  are 
various  forms,  the  most  im- 
portant being : — 

(a)  Tonographic  Methods. — 
These  consist  essentially  in 
the  use  of  a  small  mercury 
manometer,  which  records 
the  oscillations  of  the  internal 
pressure  of  the  frog's  heart  in 
relation  to  the  phases  of  its 
activity.  The  apparatus  re- 
presented by  Fig.  121  fulfils 
all  requirements  for  studying 
the  mode  in  which  the  activity 
of  the  heart  exhausts  itself, 
when  excised  from  the  animal, 
filled  with  a  nutrient  fluid, 

\  /  and  exposed  to  constant  dia- 

__J  L.  1  stolic   pressure   at   a   given 

\!^   I^  Yl  /  II  temperature.      The  heart  is 

tied  to  a  simple  cannula 
(Fig.  122,  A)  introduced  into 
the  cavity  of  the  ventricle 
through  an  opening  111  the 
sinus  venosus.  Owing  to  its 
structure,  it  is  easy  to  study 
the  effect  of  successive  liga- 
tures applied  at  different 

121.— Luciaui's  tonographic  apparatus  for   recording    heights  of  the  auricles,  when 
the  beats  of  the  heart,  when  isolate^  and^attachedtp    the  heart  ig  fixed  in  the  t(mo_ 

apparatus.       Since 


cannula    at  different    heights    of   the    auricles  (semi 
schematic),     a,  'Reservoir  of  serum  or  other  nutrient    graphic 


fluid,  closed  by  Muriotte's  method  so  as  to  keep  the   the'same  nutrient  fluid  leaves 

tilling  and  pressure  of  the  heart  constant ;  b,  valvular  ,,       ,                                    ,    -, 

apparatus,  closed  during  systole  ;  c.  tap  for  interrupting  the  heart  at  each  systole  and 

communication  between  the  reservoir  and  the  heart ;  d,  re -enters  it  at  each  diastole, 

cannula  to  which  the  heart  is  tied,  fixed  to  appara-  ^1.^   ro,,,^.,!    nf    fi,0  c^lntir»t, 

tus ;  e,  small  vessel  full  of  serum,  which  can  be  raised  L 

during  the  experiment,  so  as  to  bathe  the  whole  of  the  can    only   be   effected    slowly 

outside  of  the  heart ;/,  small  mercury  manometer,  pro-  jyyr     diffusion      through      the 

vided  with  float,  which  records  the  beats  of  the  heart  on  J                    .    /•    -i         S    ,,-,, 

the  revolving  cylinder  with  a  glass  pen.  supernatant  fluid,  and  filtra- 

tion through  the  vessel  walls. 

This  is  a  great  drawback  when  the  heart  is  to  be  kept  for  any  length  of  time 
under  constant  and  normal  conditions  of  nutrition.  Under  these  circum- 
stances it  is  necessary  to  replace  the  simple  cannula  by  the  two-way  cannula 
of  Kronecker,  figured  in  122,  B.  An  improvement  on  Kronecker's  apparatus 
is  that  of  Williams  (Fig.  123).  This  provides  for  the  circulation  of  the  nutritive 
solution,  by  the  complete  separation  of  the  fluid  which  enters,  from  that 
which  leaves,  the  heart,  by  means  of  two  valves  for  its  entrance  and  exit. 
If  the  frog's  heart  is  to  be  attached  to  the  apparatus  by  a  cannula  introduced 
into  the  ventricle  through  the  aortic  bulb,  it  is  necessary  to  supplement 
Kronecker's  irrigation  cannula  by  a  very  fine  connecting  tube,  as  shown  in 
Fig.  122  C. 

The  tonographic  method  introduced  by  Oehrwall  (1896)  is  much  simpler 
By  this  it  is  possible  to  obtain  simultaneous  tracings  of  the  activity  of  the 


IX 


CAKDIAC  MUSCLE  AND  NEKVES 


289 


right  auricle  and  the  ventricle  of  the  frog.  No  artificial  valves  are  required 
to  separate  the  vessel  containing  the  nutrient  solution  from  the  tonographie 
apparatus,  since  the  auriculp- ventricular  valves  of  the  heart  itself  are  utilised 
for  the  purpose.  As  shown  in  Fig.  124,  the  heart  is  attached  to  two  cannulae, 
one  of  which  is  tied  to  the  aorta  so  that  the  valve  is  unable  to  perform  its 
function,  the  other  to  the  sinus.  The  two  cannulae  communicate  on  the  one 
hand  with  the  vessel  containing  the  serum  or  nutritive  solution,  on  the  other 
with  two  separate  elastic  tonographs  similar  to  small  Marey's  capsules,  which 
record  the  oscillations  of  pressure  in  the  right  auricle  and  ventricle  as  trans- 
mitted by  the  air.  When  disconnected  from  the  reservoir  by  applying  a 
couple  of  pressure  forceps  at  the 

points    indicated   in  the  figure,  A  B  C 

the  heart  is  made  to  beat  in 
presence  of  a  small  quantity  of 
fluid  which  circulates  continu- 
ously. When,  on  the  other 
hand,  the  forceps  are  undamped, 
so  as  to  open  communication 
with  the  reservoir,  the  whole 
of  the  fluid  present  is  perfused 
through  the  heart.  In  the  first 
case  the  curves  recorded  by  the 
two  tonographs  are  naturally 
more  ample,  because  they  repre- 
sent the  total  pressure  developed 
within  the  heart ;  in  the  second 
case  they  are  less  ample,  because 
the  lateral  pressure  is  recorded. 

(b)  Plethysmographic  Methods. 
— These  aim  at  recording  the 
variations  in  the  volume  of  the 
cycle, 
vari- 
ous ways  to  the  heart  of  the  frog 
or  the  tortoise  by  Frangois- 
Franck,  Roy,  Gaskell,  and 
Williams.  As  shown  in  Fig. 
123,  plethysmograms  of  the 
frog's  heart  are  most  simply 
obtained  by  a  slight  modifica- 
tion in  Williams'  apparatus,  the 
heart  being  placed  in  a  small 


heart  during  the  pulsatory  cy 
They  have  been  applied  in  v£ 


FIG.  122. — A,  Simple  cannula  (Luciani)  for  frog's  heart, 
natural  size.  Consists  of  glass  tube  a,  joined  to  rubber 
tube  b,  which  connects  it  with  the  manometer,  and 
has  various  metal  rings  (c)  at  the  end,  2  mm.  apart, 
by  which  ligatures  can  be  applied  to  the  heart  at 
equal  distances.  B,  Two-way  cannula  (Kronecker) 
composed  entirely  of  metal  divided  into  two  arms, 
c,  b,  which  unite  externally  into  one  arm  d,  divided 
internally  by  a  septum  as  shown  in  section  at  e.  The 
arm  a  is  connected  with  the  chamber  for  the  serum  ; 
the  arm  b  with  the  recording  manometer.  The  metal 
wire  c  serves  as  electrode,  in  the  electrical  stimula- 
tion of  the  heart.  The  fluid  expelled  by  the  heart 
at  each  systole  is  partially  turned  out,  so  that  fresh 
serum  enters  the  heart  at  each  diastole.  C,  Cannula 
adopted  in  Williams'  apparatus.  The  same  two- 
way  cannula,  as  above,  with  the  addition  of  a  small, 
simple  metal  cannula  b,  which  is  introduced  into 
the  ventricle  by  the  bulbus  aortae. 


and  connected  with  a  Marey's 


111  a 

closed   cylinder   empty  or   filled   with 
tympanum. 

(c)  Myographic  or  Gardiographic  Methods. — By  these  we  can  record  the 
modifications  in  the  external  form  of  the  heart,  produced  by  cardiac  systole 
or  diastole.  These  methods  have  been  applied  in  a  variety  of  ways.  A  light 
lever  may  be  placed  directly  upon  the  ventricle,  or  two  levers,  one  on  the 
ventricle,  the  other  on  the  auricles,  when  the  magnified  movements  due  to 
changes  in  form  of  the  heart  (Marey's  double  myograph  for  heart  of  frog  and 
tortoise)  can  be  read  off.  An  ingenious  modification  of  this  method  is  repre- 
sented in  Fig.  125  (Marey's  pince  myographique).  Gaskell  introduced,  a 
method  of  suspension  with  which  he  obtained  interesting  results.  It  con- 
sisted in  fixing  the  heart  at  the  auriculo-ventricular  groove  by  a  screw-clamp, 
which  could  be  easily  adjusted.  The  apex  of  the  ventricle  and  tip  of  the 
auricle  are  attached  by  silk  threads  to  very  light  levers,  placed  respectively 
above  and  below  the  heart,  which  are  pulled  upward  or  downward  during 
systole,  and  record  the  magnified  movement  on  a  revolving  cylinder. 

VOL.  I  U 


290 


PHYSIOLOGY 


CHAP. 


Engelmann's  suspension  method  (Fig.  126)  is  simpler  as  well  as  more  reliable. 
The  cardiograms  which  it  records  (independent  of  the  differences  in  form 
and  amplitude  due  to  modifications  in  loading  and  length  of  lever)  always 
exhibit  marked  anatricrotism,  i.e.  the  ascending  curve  rises  to  the  summit  in 
three  shoulders,  and  falls  rapidly  in  a  single  line,  as  shown  on  Fig.  127. 
With  a  signal,  made  by  a  writing  lever,  worked  with  the  finger,  the  moment 
at  which  the  systole  and  diastole  of  the  sinus  (Ss  Sd),  the  systole  and  diastole 
of  the  auricles  (As  Ad),  the  systole  and  diastole  of  the  ventricle  (Vs  Vd), 
and  the  systole  and  diastole  of  the  bulbus  arteriosus  (Bs  Bd)  commence  can 


Fio.  123. — Left :  Williams'  tonograph  for  recording  movements  of  frog's  heart ;  excised  and 
attached  to  cannula,  inserted  into  the  ventricle  by  the  bulbus  aortae  (semi-schematic).  A 
reservoir  of  serum,  s,  communicates  from  below  with  the  cardiac  cavity  by  the  valve  v,  which 
opens  in  diastole  and  closes  in  systole.  A  second  valve  v',  which  opens  in  systole  and  closes 
in  diastole,  leads  the  serum  back  to  the  reservoir  s.  The  manometer  is  put  in  communication 
with  the  heart  by  means  of  an  arm  of  the  second  valvular  apparatus,  and  traces  on  the  revolv- 
ing cylinder  the  lateral  pressure  of  the  fluid  coming  from  the  heart.  Right :  Portion  of  Williams' 
apparatus  substituted  for  the  little  cup  that  encloses  the  heart,  when  it  is  desired  to  see  the 
changes  of  volume  during  the  beats.  If  the  small  chamber  containing  the  heart  is  left  empty, 
and  the  end  of  the  curved  arm  of  the  manometer  connected  with  a  highly  sensitive  Marey's 
tambour,  the  apparatus  is  converted  into  a  cardiac  plethysmograph. 

be  accurately  enough  determined.  The  result  of  these  experiments  (according 
to  Engelmann)  is  that,  generally  speaking,  the  movements  Vs  and  Vd  are  the 
only  ones  of  which  the  commencement  is  clearly  traced  in  the  cardiogram. 
The  beginning  of  Vs  coincides  with  the  beginning  of  the  second  rapid  rise, 
and  of  Vd  with  that  of  the  rapid  descent  from  the  summit  of  the  curve.  By 
using  the  signal,  however,  it  is  possible  (taking  the  average  of  a  good  number 
of  experiments)  approximately  to  determine  the  other  periods  of  the  pulsatory 
cycle,  and  to  estimate  their  duration  in  hundredths  of  a  second.  (Engelmann, 
"  Observations  et  experiences  sur  le  coeur  suspendu,"  Arch.  Neerlandaises.  voL 
xxvi.) 

B.  Warm -Blooded  Animals. — The  methods  employed  for  the  graphic 
registration  of  oscillations  of  pressure  and  volume  of  the  heart  in  situ, 
were  discussed  in  the  chapter.  Changes  in  form  may  be  recorded  by  the 


IX 


CARDIAC  MUSCLE  AND  NERVES 


291 


method  of  multiple  suspension  from  writing  levers,  attached  by  threads  to 
different  parts  of  the  heart  (Francois-Franck,  Knoll).     Various  methods  have 


FIG.  124.  —  Oehrwall's  tonograph.  c,  Glass  bulb  to  cover  outside  of  heart;  1>,  reservoir  of 
nutrient  fluid  ;  c,  tonograph  for  right  auricle ;  '/,  tonograph  for  ventricle ;  e,  /,  clips  for 
altering  communication  with  reservoir. 

been  adopted  in  the  study  of  the  mammalian  heart,  independent  of  any 
cerebrospinal  nervous  influence  and  of  the  systemic  circulation,  with  the 
object  of  more  or  less  completely  isolating  the-  cardie-pulmonary  circulation 


FIG.  125. — Marey's  myograph  for  recording  movements  of  frog's  heart  in  situ.  This  is  a  sort  of 
clip  formed  of  two  spoons  supported  by  two  curved  arms  at  right  angles,  one  fixed,  the  other 
movable.  The  latter  carries  a  horizontal  lever,  provided  at  the  end  with  a  point,  writing  on 
a  smoked  cylinder.  The  movable  spoon,  which  is  displaced  at  each  systole,  is  brought  back 
to  its  original  position  at  each  diastole  by  a  fine  rubber  thread,  fixed  by  a  pin  to  the  board  on 
which  the  frog  is  fastened.  Both  spoons  are  connected  with  wires,  by  which  various  kinds  of 
electrical  stimuli  can  be  transmitted  to  the  heart.  The  exact  moment  of  stimulation  is 
recorded  in  the  cylinder  by  a  Deprez  signal. 

(Newell,  Martin,  H.  E.  Hering,  Hedoii  and  Arrous,  and  others).  Langendorff 
(1895)  was  the  first  who  succeeded  by  the  method  of  direct  transfusion  through 
the  coronary  arteries  in  keeping  the  mammalian  heart  alive  for  any  consider- 
able time,  when  completely  isolated  and  removed  from  the  body  (under  which 


292 


PHYSIOLOGY 


CHAP. 


conditions,  without  special  treatment,  it  speedily  ceases  to  beat).     By  means 

of  a  cannula  "tied  to 
the  aorta,  in  the  direc- 
tion of  the  heart,  he 
caused  blood  or  other 
nutrient  solutions  to 
circulate  at  a  tempera- 
ture of  38°  C.  under  a 
pressure  corresponding 
to  the  normal  pressure 
of  the  aorta.  The  fluid 
keeps  the  semilunar 
valves  closed,  circulat- 
ing through  the  coron- 
ary system  of  the  heart, 
and  flowing  out  again 
through  the  opening  in 
the  right  auricle.  The 
cardiac  cavity  remains 
empty.  A  heart  thus 
artificially  fed  is  cap- 
able of  continuing  its 
activity  almost  nor- 
mally for  many  hours. 
The  graphic  record  of 
its  movements  can  be 
taken  by  means  of  sus- 
pension, or  (after  oc- 
cluding the  veins  of 
the  right  auricle)  by  a 
manometer  applied  to 
the  pulmonary  artery 
(Siewert,  1904). 


FIG.  126.  —  Engelmann's  myograph  for  recording  beats  of  frog's 
heart  in  situ,  when  suspended  from  the  apex  by  a  thread 
connected  with  a  highly  sensitive  lever.  The  apparatus  is  a 
two-armed  lever,  one  arm  of  which  is  attached  to  a  tine  silk 
thread,  the  other  to  a  long  straw  or  strip  #f  aluminium,  which 
magnifies  the  movements  of  the  writing  point  on  a  smoked 
surface.  At  the  end  of  the  thread  is  a  fine  glass  hook,  with 
sharp  point,  which  is  inserted  into  the  tip  of  the  apex,  after 
cutting  the  fraenum  by  which  the  two  layers  of  the  pericardium 
are  united  dorsally. 


II.  The  fact  that 
it  impossible  to  keep 
the  isolated  heart  of  different  animals  alive  for  a  comparatively 
long  period  has  been  used  as  the  start- 
ing-point for  a  series  of  researches  on  the 
nutritive  medium,  or  external  chemical 
conditions,  necessary  to  its  survival. 

This  work  has  familiarised  us  with 
the  so-called  physiological  solutions, 
which  are  artificial  nutrient  fluids, 
capable  (at  least  for  a  certain  time)  of 
replacing  the  blood,  since  they  contain  a  fc 
all  the  elements  necessary  for  sustaining  FIG.  i27.-cardiograms  taken  from 

.,        •..[,        0,1        i  mi        •  fr°8  by  Engelmanns  method,    a, 

the  llle  OI  the  heart.  I  he  importance  Commencement  of  ventricular 
f\f  fViia  anKianf  ovr>aarle  fV»o  lirnifa  r»f  ^-V»c»  systole  ( Vs) ;  b,  commencement  of 

ol  tins  subject  exceeds  the  limits  01  uhe  diastoieVd);c,  curves  of  a  tuning- 
present  chapter,  for  it  may  logically  Snjhich  vibrates  10  times  per 
be  concluded  that  artificial  fluids  which 

are  capable  of  sustaining  the  vitality  of  the  excised  heart  will 
also  maintain  the  vitality  of  other  organs  or  isolated  tissues,  or  are, 


ix  CAEDIAC  MUSCLE  AND  NEKVES  293 

at  any  rate,  innocuous  to  the  body  as  a  whole,  when  introduced 
into  the  circulation. 

We  should,  a  priori,  expect  the  best  effects  to  result  from  those 
solutions  which  in  their  chemical  composition  most  closely 
resemble  the  complex  constitution  of  blood — the  natural  food  of 
all  the  tissues.  In  practice,  however,  this  is  the  case  only  to  a 
limited  extent. 

A  point  much  discussed  by  the  various  investigators  has  been 
'the  importance  of  oxygen  in  these  physiological  solutions.  No 
one,  however,  now  doubts  that  it  represents  an  element  indis- 
pensable to  the  survival  of  the  heart. 

Von  Humboldt  (1797)  was  the  first  to  emphasise  the  vivifying 
power  of  oxygen  in  the  excised  heart  of  the  frog.  Following  his 
initiative,  Castell  (1854)  made  a  systematic  series  of  researches  in 
the  same  direction.  He  found  that  a  frog's  heart  placed  in  a  moist 
chamber  at  16-20  E.  went  on  beating  for  three  hours  in  ordinary 
air,  for  twelve  hours  in  the  presence  of  oxygen,  for  about  one  hour 
in  presence  of  hydrogen  or  nitrogen,  for  a  few  minutes  only  in 
presence  of  carbonic  acid. 

In  our  own  researches  on  the  excised  frog's  heart  (1873),  con- 
nected with  a  manometer,  and  filled  with  serum  of  pig  or  rabbit, 
we  observed  that  the  frequency  and  force  of  the  beats  augmented 
each  time  the  serum  already  used  was  reinforced  by  fresh 
oxygenated  serum ;  the  rhythm  slowed  down  and  weakened  when 
the  heart  was  made  to  float  in  oil.  The  vivifying  action  of 
oxygen  on  the  frog's  heart  was  confirmed  by  Kossbach  and  King. 

Langendorff  (1884)  experimented  with  the  asphyxiated  heart, 
and  noted  that  it  absorbed  oxygen  with  great  rapidity,  so  that  the 
blood  introduced  into  it  suddenly  assumed  a  venous  hue. 

Yeo  (1885)  made  the  reduction  of  oxyhaenioglobin  by  the 
frog's  heart  the  subject  of  a  methodical  research.  He  found  that 
this  reduction  increased  with  the  work  done  by  the  heart.  Heffter 
and  Albanese  confirmed  the  fact  that  the  presence  of  oxygen  is 
indispensable  to  the  maintenance  of  cardiac  activity. 

The  most  exact  and  minute  researches  on  asphyxia  and  the 
revivification  of  the  excised  frog's  heart  are,  however,  due  to 
Oehrwall  (1893-97).  He  studied  the  mode  of  onset  and  the 
duration  of  asphyxia  in  the  frog's  heart  filled  with  blood  or  serum, 
through  which  a  solution  of  sodium  chloride  or  of  some  indifferent 
gas  was  circulated,  as  well  as  revival  by  the  substitution  of 
oxygenated  for  asphyxiated  blood,  or  by  the  direct  action  of  air 
and  oxygen. 

The  importance  of  oxygen  to  the  function  of  the  heart  in  warm- 
blooded animals  was  shown  by  Fano  (1889-90)  on  the  embryonic 
chick's  heart,  isolated  on  the  second  or  third  day  of  incubation. 

A.  Porter  (1898)  succeeded  in  keeping  the  isolated  mammalian 
heart  alive  for  many  hours  in  the  presence  of  blood  serum  and 


294  PHYSIOLOGY  CHAP. 

oxygen  under  a  pressure  of  two  atmospheres.  But  the  same  effects 
may  be  more  simply  obtained  by  the  artificial  circulation  through 
the  coronary  system  of  a  physiological  solution  (to  be  described 
below)  saturated  with  oxygen,  or  even  with  air.  It  is  essential  in 
both  cases  that  the  fluid  should  not  stagnate  in  the  vessels. 

Eusch  (1898)  found  that  the  circulation  of  serum  instead  of 
defibrinated  blood  necessitated  a  higher  pressure  to  make  it  circu- 
late with  greater  velocity,  in  order  to  provide  the  heart  with  the 
quantum  of  oxygen  necessary  to  its  activity. 

Other  researches  on  the  necessity  of  oxygen  to  the  survival  of 
the  mammalian  heart  were  instituted  by  Strecker  (1900),  and 
more  particularly  by  Magnus  (1902),  who  was  the  first  to  circulate 
gases  instead  of  fluids  through  the  coronary  arteries  of  the  isolated 
cat's  heart.  He  found,  on  injecting  oxygen,  that  the  heart  beat 
for  about  an  hour.  Its  arrest  is  due  to  the  permeability  of  the 
vessel  walls  by  gas.  He  saw  that  when  hydrogen  was  injected  in 
place  of  oxygen,  the  heart  continued  to  beat  for  about  half  an 
hour,  while  it  stopped  after  a  few  minutes  when  carbonic  acid  was 
injected.  The  beneficent  action  of  the  circulating  hydrogen 
depends,  therefore,  upon  the  elimination  of  the  carbonic  acid 
developed  by  the  heart  during  its  activity ;  but  hydrogen  is  not 
sufficient  to  keep  it  going  for  a  long  time,  and  the  heart  ceases  to 
beat  after  it  has  exhausted  all  the  oxygen  which  it  holds  in  loose 
combination. 

Winterstein  controlled  the  importance  of  oxygen  by  circulating 
Einger's  solution,  charged  sometimes  with  oxygen,  sometimes  with 
nitrogen,  through  the  coronaries  of  the  isolated  cat's  and  rabbit's 
heart.  He  came  to  the  following  conclusions : — 

(a)  The  mammalian  heart  requires  external  oxygen  to  main- 
tain its  activity.  Its  rhythm  alters  and  it  soon  comes  to  a  stand- 
still, if  nitrogen  is  substituted  for  oxygen. 

(5)  If  after  a  definite  lapse  of  time  the  current  of  oxygen  is 
re-established,  the  heart  is  able  to  beat  again. 

(c)  It  is  possible  to  reproduce  the  state  of  asphyxia  repeatedly 
in  the  same  heart,  and  in  the  above  experiments  it  was  observed 
that  the   time   necessary  for   reproducing   asphyxial  arrest   was 
shorter  than  that  required  for  its  first  incidence. 

(d)  The  immediate  condition  of  asphyxial  arrest  appears  to 
consist  in  the  consumption  of  internal  oxygen  that  takes  place 

f  during  cardiac  activity. 

/         Does  the  function  of  free  oxygen,  as  the  necessary  condition  of 

/    the  rhythmic  activity  of  the  heart,  consist  in  the  oxidation  of  the 

j     muscular  biogen  which  produces  the  alternate  contractions  and 

expansions  of  the  myocardium,  or  does  it  rather  lie  in  the  oxidation 

of  the  toxic  katabolic  products  that  result  from  the  metabolism  of 

\     the  muscle,  transforming  them  into  innocuous  substances,  readily 

\    eliminated  ? 


ix  CARDIAC  MUSCLE  AND  NERVES  295 

Arguments  in  favour  of  this  last  hypothesis  are  not  wanting, 
but  the  first  must  also  be  admitted  as  credible,  until  it  is  directly 
contradicted  by  experiment. 

C.  Ludwig  (1868)  was  the  first  who  employed  the  method  of 
artificial  circulation  in  excised  organs,  in  studying  their  survival. 
The  primitive  physiological  solution,  consisting  of  a  dilute  solution 
of  sodium  chloride  (0*50-0'75  per  cent),  was  largely  used  by  him 
and  his  school  as  a  substitute  for  defibrinated  blood,  in  experi- 
menting on  the  metabolism  of  excised  organs.  A  little  serum 
added  to  the  saline  will  keep  up  the  vitality  of  the  excised  heart 
of  a  frog  for  a  very  long  time. 

Kronecker  and  Stirling  (1875),  however,  found  that  the  beats 
of  a  frog's  heart  tied  by  the  ventricle  to  a  cannula  (Bowditch's 
preparation)  were  retarded,  and  its  activity  brought  to  a  standstill 
in  a  short  time,  when  a  simple  0*6  per  cent  solution  of  NaCl  was 
substituted  for  the  blood  or  serum.  Salt  water,  therefore,  does 
not  in  itself  contain  the  whole  of  the  chemical  constituents  necessary 
for  the  maintenance  of  cardiac  activity. 

Merunovics  (1877)  tried  the  effect  of  watery  solutions  made  of 
the  ash,  or  the  alcoholic  extract  of  serum,  which,  he  found,  main- 
tained cardiac  activity  better  than  the  simple  solution  of  sodium 
chloride.  He  attributed  this  effect  to  the  beneficial  action  of  the 
alkaline  carbonate. 

Stienon  (1878),  following  Merunovics,  observed  that  the 
difference  between  the  action  of  the  fresh  serum  and  its  filtrate, 
after  this  had  been  boiled,  consisted  in  the  more  limited  capacity 
of  the  latter  to  revive  a  cardiac  preparation  of  which  the  activity 
had  been  reduced  to  its  minimum  by  prolonged  treatment  with 
saline.  He  also  found  that  neutralisation  of  the  normal  alkalinity 
of  the  serum  with  acid  diminished  its  beneficial  action  on  the 
heart.  Lastly,  he  demonstrated  that  a  solution  of  sodium  chloride 
rendered  alkaline  with  O'l  per  cent  sodium  carbonate  is  capable  of 
restoring  the  activity  of  a  heart  that  had  previously  been  arrested 
by  treatment  with  salt  solution.  Gaule,  later  on,  found  it  more 
useful  for  this  purpose  to  add  a  small  quantity  of  soda  instead  of 
the  carbonate,  pointing  out  that  the  alkali  is  neutralised  during 
cardiac  activity  by  the  development  of  carbonic  acid,  which  converts 
it  into  the  carbonate. 

Martius  (1882)  explained  the  beneficial  action  of  serum  by 
assigning  a  greater  importance  to  its  organic  than  to  its  inorganic 
constituents,  and  to  serum  albumin  in  particular,  assuming  that 
the  development  of  cardiac  energy  was  dependent  on  the  presence 
of  some  nutrient  matter  in  the  circulating  fluid. 

Against  this  positive  assumption,  however,  we  must  set  the 
work  of  Ringer,  who  made  a  series  of  experiments  to  show  that 
the  addition  of  calcic  or  potassic  salts  to  the  NaCl  solution 
effectively  prolongs  cardiac  activity,  as  has  since  been  confirmed 


296  PHYSIOLOGY  CHAP. 

by  all  who  have  taken  up  this  subject.  Einger's  solution 
consists  of — 

100   c.c.  of  a  6  per  cent  solution  of  NaCl 
1         „       1  „  XaHCO3 

„       1         ,,  „  CaCl2 

075    „       1         „  „  KC1 

Locke  (1895)  showed  by  new  work  that  the  addition  of  a  small 
quantity  of  glucose  to  Einger's  solution  rendered  it  more  capable 
of  maintaining  cardiac  activity. 

Gothlin,  under  Oehrwahl's  direction,  has  recently  (1902) 
carried  out  some  detailed  experiments  on  the  chemical  conditions 
of  cardiac  activity  in  the  excised  heart  of  the  frog.  He  prepared 
a  complex  solution  of  mineral  substances,  including  all  those 
which  chemical  analysis  has  shown  to  be  present  in  blood  serum, 
in  the  following  proportions  : — 

NaCl  .  .  .  0-65  percent.  Cl  .  .  .  .  O'Ol  percent. 
NaHC03  .  .  0-1  „  CaCl2  .  .  .  0-0065  „ 

Na2HP04       .        .     0-0009        „  XaH2P04        .         .     0-0008'       „ 

He  found  that  on  replacing  the  blood  by  this  solution  cardiac 
activity  was  maintained  unaltered  for  many  hours.  The  pro- 
portions in  which  the  different  salts  enter  into  solution  are  by  no 
means  unimportant.  On  substituting  Einger's  solution  for  the 
above,  both  rhythm  and  type  of  beat  were  modified.  Gothlin 
further  saw,  on  preparing  solutions  in  which  one  or  other  of  the 
constituents  predominated  (with  the  object  of  determining  the 
influence*  of  each  upon  cardiac  activity),  that  the  results  indicated 
all  to  be  more  or  less  necessary  to  its  maximal  prolongation. 

In  a  second  series  of  researches  he  proposed  to  determine  on 
what  the  great  difference  between  the  survival  period  of  a  heart 
treated  with  his  solution,  composed  solely  of  inorganic  substances, 
'and  that  of  a  heart  treated  with  normal  blood,  depends.  As  regards 
the  importance  of  the  erythrocytes  and  of  haemoglobin  the  fact  he 
discovered  is  worth  noting,  that  a  haemolytic  fluid  (i.e.  one  which 
contains  dissolved  haemoglobin)  is  injurious  rather  than  beneficial. 
He  explained  the  toxic  action  of  this  dissolved  haemoglobin  to 
consist  in  its  combining  with  the  lime-salts  of  the  serum,  so  that 
they  are  removed  from  the  heart,  which  requires  lime  salts  electro- 
lytically  dissociated  in  the  form  of  Ca-ions.  In  fact,  he  found  that 
the  subsequent  addition  of  lime  salts  renders  haemolytic  blood 
innocuous. 

In  other  experiments  he  found  that  after  weakening  the  heart 
with  his  saline  solution,  he  could  restore  its  activity  by  perfusing 
it  with  a  new  complex  solution  consisting  half  of  serum  of  ox 
blood,  half  of  the  saline  solution.  He  concluded  that  serum  must 
contain  a  substance  capable  of  exerting  this  beneficial  action 
on  the  heart,  and  proposed  to  ascertain  experimentally  which  it 


ix  CAEDIAC  MUSCLE  AND  NERVES  297 

was   of  the   numerous   organic    substances   present.      He   tested 
glucose,  serin,  and  paraglobulin  with  negative  results. 

Baglioni  (1905-6)  was  more  fortunate  in  his  experiments  on  the 
isolated  heart  of  Selachians.  He  knew  from  the  previous  researches 
of  Stadeler  and  Frerichs,  and  of  v.  Schroder,  that  the  blood  of 
these  animals  is  very  rich  in  urea  dissolved  in  the  plasma. 
According  to  v.  Schroder  the  blood  of  the  Scyllium  contains  on  an 
average  2'61  per  cent  urea.  This  facts  explains  the  high  values 
'of  the  molecular  concentration  of  the  blood  in  these  fishes,  which 
corresponds  to  a  solution  of  about  3*5  per  cent  of  NaCl.  Straub 
had  already  found  that  a  saline  solution  of  this  concentration  was 
incapable  of  keeping  the  excised  heart  of  these  animals  alive,  even 
for  a  short  time — an  observation  contrary  to  what  had  been 
observed  on  the  hearts  of  frogs  and  other  poikilotherniic  animals. 
Baglioni  discovered  that  it  is  possible  to  keep  the  isolated  Selachian 
heart  alive  for  a  prolonged  period  by  treating  it  with  a  solution 
containing  a  definite  amount  of  urea.  He  found  the  most  effective 
solution  to  be  one  that  contained  2  grrns.  of  urea,  and  2  grins,  of 
sodium  chloride  in  100  c.c.  of  tap  water,  which  invariably  yields 
traces  of  lime  salts.  He  further  tried  to  determine  the  specific 
action  of  urea,  and  concluded  from  his  experimental  results  that  it 
promotes  the  contraction  of  the  muscle  cells,  while  larger  doses 
arrest  the  heart  in  systole.  Sodium  chloride,  on  the  contrary, 
promotes  expansion  of  the  muscle  cells,  and  large  doses  cause 
diastolic  arrest. 

Lambert  (1905)  confirmed  the  favourable  action  of  urea  on  the 
frog's  heart ;  Baglioni  and  Federico  (1906)  on  that  of  the  toad. 
In  these  animals,  also,  urea  increases  the  intensity  and  duration  of 
the  systolic  phase. 

Analogous  observations  were  made  on  the  isolated  heart  of 
warm-blooded  animals  Gross  (1903)  carried  out  a  methodical 
series  of  experiments  on  the  action  of  the  various  components  of 
Ringer's  solution,  confirming  the  results  already  obtained  for  the 
frog's  heart.  The  antagonism  in  the  action  of  potassium  and 
calcium  ions  was  marked.  The  former  exerted  a  systolic,  the 
latter  a  diastolic  action ;  in  large  doses  the  first  arrested  the 
heart  in  systole,  the  second  in  diastole. 

Langendorff  and  his  pupils,  confirming  the  necessity  of  the 
presence  of  lime  salts,  studied  the  action  of  dissolved  haemoglobin, 
when  they  found  that  only  certain  mammalian  hearts  behave  like 
that  of  the  frog.  The  hearts  of  cat  and  dog  do  not  to  any  marked 
extent  exhibit  toxic  effects  with  dissolved  haemoglobin,  while  that 
of  the  rabbit  behaves  like  the  frog's  heart.  In  explanation  of  this 
difference,  Langendorff  points  out  that  the  rabbit's  erythrocytes 
contain  a  much  larger  quantity  of  potassium  salts  than  those  of  the 
dog  or  cat.  Supposing  that  a  large  amount  of  potassic  salts  are 
diffused  in  the  rabbit's  serum  along  with  the  haemoglobin,  these 


-  * 


298  PHYSIOLOGY  CHAP. 

might  exert  a  toxic  action  upon  the  cells  of  the  myocardium.  The 
beneficial  effects  of  adding  lime  salts  to  the  haemolytic  fluid  may 
be  explained  by  the  antagonism  between  the  salts  of  calcium  and 
potassium. 

Bachmann  (1906),  under  Oehrwall's  direction,  carried  out  a 
fresh  series  of  researches  upon  the  action  on  the  isolated 
mammalian  heart  of  the  organic  nitrogenous  substances  present 
in  normal  blood,  adding  it  in  known  doses  to  Locke's  solution, 
and  perfusing  it  by  Langendorff's  method.  He  studied  the  action 
of  urea,  of  ammonium  carbonate,  of  sodic  hippurate,  of  sodic 
urate,  of  creatine,  of  hypoxanthine,  of  xanthine,  of  allantoin. 
Generally  speaking,  he  found  that  these  substances,  in  doses 
approximately  equal  to  their  proportions  in  normal  blood, 
exercised  only  a  slight  and  parallel  action  upon  the  heart,  in- 
creasing the  amplitude  of  the  systole.  Some  of  them  further 
accelerated  the  frequency  of  rhythm,  in  particular  urea,  which 
agrees  completely  with  the  results  of  Baglioni. 

Special  mention  must  be  made  of  the  recent  attempts  to 
revive  the  dead  heart  of  warm-blooded  animals.  Kuliabko 
(1901-3)  was  the  first  to  revive  the  heart  of  animals  three  or  four 
days  after  death  (the  bodies  being  kept  meantime  in  ice),  by 
perfusing  the  coronaries  with  Einger- Locke  solution.  Seven 
days  after  death  it  was  found  impossible  to  revive  the  normal 
pulsations  of  the  whole  heart ;  fibrillary  contractions  could,  how- 
ever, be  observed  in  the  auricles.  The  heart  of  an  infant  that 
had  died  of  pneumonia  was  made  to  beat  again  after  twenty  hours.  J 

H.  E.  Hering  continued  the  researches  of  Kuliabko  on  the 
hearts  of  rabbit,  cat,  and  monkey.  In  a  monkey  found  dead  in 
the  laboratory  he  succeeded,  four  and  a  half  hours  later,  in 
reviving  the  heart,  left  in  situ.  The  body  was  then  frozen.  On 
the  following  day,  i.e.  24  hours  and  32  minutes  after  the  animal 
had  been  found  dead,  the  heart  was  revived  for  the  second  time. 
The  carcase  was  again  frozen,  and  a  third  revival  successfully 
attempted  53  hours  and  43  minutes  after. 

The  same  experiments  of  revival  were  attempted  on  the 
human  adult  heart.  Dencke  and  Adam  succeeded  in  obtaining 
pulsations  in  the  heart  of  a  criminal  forty-three  years  old,  13 
minutes  after  his  execution. 

More  recently  Hering  succeeded,  with  Einger's  solution  alone, 
in  reviving  the  heart  of  a  young  criminal  of  thirty-five,  eleven 
hours  after  death,  and  was  able  to  use  it  for  experiment  for 
three  hours.  It  is  interesting  to  note  that  both  Dencke  and 
Hering  assert  that  they  found  no  difference  between  the  human 
and  other  mammalian  hearts  as  regards  their  reaction  to  circulating 
fluids. 

TT^-The  most  generally  noted  and  recognised  fact  is  that  the 
conditions  of  rhythmical  cardiac  activity  are  located  in  the 


IX 


CAKDIAC  MUSCLE  AND  NEKVES 


299 


heart  itself,  and  are  independent  of  the  connections  which  unite 
it  by  the  afferent  nerves  with  the  cerebrospinal  axis.  Galen  was 
aware  that  the  excised  heart  is  able  to  beat  for  a  considerable 
time.  Under  favourable  conditions  of  moisture,  temperature, 
irrigation  with  blood  and  other  nutrient  fluids,  and  in  presence 
of  oxygen,  the  excised  heart,  not  only  of  cold-blooded  animals  but 
of  mammals  also,  may  continue  its  functions  for  many  hours. 

TheearlierHallerian 
'doctrine,  which  saw  in 
this  fact  a  proof  of  the 
rhythmic  activity  of 
cardiac  muscle  inde  - 
pendent  of  nerves  and 
nerve-centres,  was  dis- 
allowed after  it  had 
been  shown  by  Bichat 
and  J.  Mliller  that  the 
peripheral  sympathetic 
ganglia  function  as  in- 
dependent centres  in  the 
organs  of  vegetative  life, 
while  Eeniak  (1844), 
Ludwig  (1848),  and 
Bidder(1852)discovered 
a  nerve-plexus  rich  in 
ganglion  cells  in  the 
frog's  heart. 

Eemak  demonstrated 
the  existence  of  a  con- 
spicuous accumulation 
of  ganglion  cells  at  the 
mouth  of  the  sinus 
venosus  in  the  right 
auricle  of  the  frog's 
heart.  Ludwig  de- 
scribed other  ganglionic 
elements  in  the  region  of  the  interauricular  septum.  Bidder 
discovered  two  other  masses  of  ganglion  cells  near  the  auriculo- 
ventricular  groove  (Fig.  128).  Nothing  after  these  discoveries 
could  be  more  natural  than  to  ascribe  the  function  of  excitatory 
centres  of  the  rhythmic  peristaltic  movements  of  the  heart  to 
these  intracardiac  ganglia. 

Certain  well-known  experiments  of  Stannius(1852)  gave  fresh 
sanction  to  this  theory  of  the  intracardial  ganglionic  centres, 
although  they  received  various  and  even  contradictory  interpreta- 
tions. In  his  experiments  on  the  frog's  heart  Stannius  discovered 
two  facts  which  appeared  to  be  of  extreme  interest : — - 


FIG.  128.  — Interauricular  septum  of  frog's  heart.  (Bidder.) 
a.,  Muscular  fibres ;  b,  endocardium  ;  c,  free  border  of 
septum  ;  d,  d,  ventricular  walls  ;  e,  f,  right  and  left 
branches  of  cardiac  vagus,  with  partial  decussation  ;  h,  h', 
anterior  and  posterior  nerves  to  septum,  with  numerous 
ganglion  cells,  particularly  at  points  k,  k' ;  I,  ?',  ganglia 
near  the  auriculo-ventriculur  border  (Bidder's  ganglia). 


300  PHYSIOLOGY  CHAP. 

(a)  When  a  ligature  is  applied  at  any  height  of  the  auricle, 
between  the  opening  of  the  sinus  venosus  into  the  right  auricle, 
and  the  region  nearest  the  auriculo- ventricular  junction,  arrest  of 
the  heart  is,  ipso  facto,  produced  in  all  parts  below  the  ligature, 
while  above,  in  the  sinus  and  the  part  of  the  auricle  that  is  not 
blocked,  the  rhythm  is  undisturbed. 

(b)  When    a    second    ligature    is   applied    to   the   auriculo- 
ventricular  groove  in  a  heart  that  has  been  arrested  by  the  first 
ligature,  the  ventricle  begins  to  beat  again,  even  though  much 
more   slowly  than  the  normal,   while   the  auricles   still    remain 
motionless. 

Eckhard  (1858-60)  showed  that  practically  the  same  results 
were  obtained  by  making  incisions  in  the  frog's  heart,  as  by  the 
method  of  Stannius.  At  the  same  time  he  denied  their  supposed 
constancy,  and  found  a  great  variety  of  effect  both  from  ligation 
and  from  sections,  in  accordance  with  fluctuations  of  external 
temperature,  and  the  varying  sensitivity  of  the  preparation,  and 
more  particularly  of  the  different  regions  operated  on.  He 
confirmed  the  fact  already  observed  by  Heidenhain  that  the 
arrest  of  the  heart  produced  by  the  ligature  or  section  is  not 
permanent,  for  the  beats  invariably  recommence  after  a  longer  or 
shorter  pause  (lasting  from  a  few  minutes  to  an  hour). 

None  of  the  several  hypotheses  advanced  in  explanation  of 
these  facts  will  bear  searching  criticism.  Eckhard  accounts  for 
the  effect  of  the  first  Stannius  ligature  on  the  rhythm  of  the 
heart  by  assuming  a  sort  of  nceud  vital,  represented  by  Kemak's 
ganglia.  To  explain  the  effects  of  the  second  ligature,  he  assumes 
that  it  provokes  a  certain  excitation  of  Bidder's  ganglia.  Eemak's 
ganglia  must  function  automatically,  since  the  spontaneous  move- 
ments of  the  heart  cease  when  their  influence  is  cut  out ;  Bidder's 
ganglia  must  be  reflex  in  function,  since  the  stimulus  of  ligaturing 
the  auriculo-ventricular  junction  is  required  to  throw  them  into 
activity.  When,  in  fact,  instead  of  ligation,  an  incision  is  made 
in  this  region,  which  would  not  have  much  excitatory  effect  on 
Bidder's  ganglia,  permanent  standstill  of  the  ventricle,  usually 
preceded  by  only  8-10  beats,  is  produced. 

This  theory,  which  involves  a  specific  differentiation  of  the 
cardiac  ganglia  into  automatic  and  reflex,  is  unsatisfactory.  In 
order  to  defend  it,  we  must  assume  that  the  upper  Stannius 
ligature  has,  for  its  sole  effect,  the  physiological  exclusion  of 
Kemak's  automatic  ganglia,  and  that  the  lower  ligature  on  the 
contrary  causes  the  reflex  excitation  of  Bidder's  ganglia. 

We  attacked  this  question  in  Ludwig's  laboratory  in  1872,  and 
saw  that  when  the  ligature  was  applied  to  the  frog's  heart,  after 
the  insertion  of  a  simple  cannula,  with  its  point  projecting  into 
the  ventricle,  the  same  effects  were  obtained  as  with  the  Stannius 
ligatures.  But  when  the  cannula  was  filled  with  fresh  rabbit's  or 


IX 


CAEDIAC  MUSCLE  AND  NEKVES 


301 


sheep's  serum,  by  which  a  certain  pressure  was  exerted  on  the  in- 
terior of  the  frog's  heart,  it  began  to  beat  again  vigorously,  regardless 
of  the  point  at  which  the  ligature  was  applied.  In  order  to  study 
the  course  of  the  heart's  action  under  these  conditions  we  connected 


FIG.  129. — Paroxysm  in  form  of  ascending  staircase,  shown  by  frog's  heart,  filled  with  sheep's 
serum,  and  tied  at  auriculo-ventricular  groove,  immediatefy  after  attachment  to  tonographic 
apparatus.  (Luciani.) 

the  cannula  with  the  excised  frog's  heart  to  a  small  recording 
mercury  manometer  (Fig.  121),  and  then  obtained  the  curves  of 
three  distinct  and  quite  characteristic  phenomena,  representing 


FIG.  130. — Tetaniform  paroxysm  presented  by  frog's  heart  already  attached  to  tonographic 
apparatus,  as  the  effect  of  a  second  ligatm-e  2  mm.  below  the  auriculo-ventricular  groove. 
(Luciani.) 

three   different   phases   of   cardiac   activity,   which    precede    the 
exhaustion  of  the  heart. 

The    first    phenomenon    may    be    termed    the    "  paroxysm " 


FIG.  131. — Tetaniform  paroxysm  commencing  at  «,  after  ligature  of  auricles,  converted  at'fr  into 
an  ascending  staircase,  by  the  momentary  opening  of  the  valve  of  the  tonographic  apparatus. 
(Luciani.) 

(accesso),  and  consists  in  a  sudden  increase  of  cardiac  muscular 
tonus  in  conjunction  with  great  frequency  of  beat.  With 
the  progressive  diminution  of  tone  the  beats  become  less 
frequent,  but  are  at  the  same  time  more  ample  in  diastole, 
since  the  presystolic  filling  of  the  ventricle  steadily  increases. 


302 


PHYSIOLOGY 


CHAP. 


This  fact  is  shown  (owing  to  the  special  character  of  the  apparatus) 
in  the  curve  of  Fig.  129  as  an  ascending  staircase,  produced  by  the 
progressive  increase  not  of  systole,  but  of  diastole,  in  proportion 
as  the  tone  of  the  myocardium  diminishes.  For  when  a  second 
ligature  is  applied  to  the  auricles,  the  heart  being  already  connected 
with  the  recording  apparatus,  the  tracing  assumes  a  tetanic  form, 
and  the  beats,  as  they  become  more  excursive,  rise  above  a  regularly 
descending  line,  which  is  the  exact  expression  of  the  progressive 


Fir;.  ISSL—Tetaniform  paroxysm  commencing  at  a  after  provisory  ligature  of  auricles ;  converted 
at  b  into  slightly  ascending  staircase,  the  beats  becoming  less  frequent,  after  removal  of 
ligature.  (Luciani.) 

decrease  in  tonicity  (Fig.  130).  If,  after  applying  the  second 
ligature  to  the  auricle,  the  valve  which  separates  the  heart  from 
the  vessel  of  serum  is  opened,  the  beats  which  accompany  the 
attack  assume  the  form  of  an  ascending  staircase,  as  in  Fig.  129, 
which  bears  out  our  interpretation  (Fig.  131).  Practically  the 
same  result  is  obtained  if  the  ligature  is  applied  soon  after  the 
paroxysm  has  commenced  (Fig.  132). 


F;G.  133.—  Periodic  rhythm  shown  by  frog's  heart  tied  at  the  auricles,  2  nun.  above  the 
auriculo-ventricular  groove,  tilled  with  rabbit's  serum  and  attached  to  tonographic  apparatus 
of  Fig.  121.  (Luciani.)  The  figure  shows  four  periods  of  regular  increase,  both  in  number  of 
beats  in  groups  and  in  duration  of  pause.  The  divisions  along  the  abscissa  represent 
intervals  of  1  second. 

The  phenomenon  of  "paroxysm,"  which  shows  that  the 
ligature  applied  at  different  heights  of  the  auricles  (in  conjunction 
with  the  action  of  serum  and  of  a  certain  degree  of  pressure) 
invariably  acts  not  merely  by  separating,  but  also  by  contusing 
and  irritating  the  walls  of  the  heart,  seems  to  us  the  most  direct 
refutation  of  the  doctrine  of  the  twofold  nature  of  the  cardiac 
ganglia. 

When  the  paroxysm  is  over,  a  new  phenomenon  appears  which 
we  have  termed  periodic  rhythm,  in  which  the  cardiac  pulsations 


IX 


CAEDIAC  MUSCLE  AND  NEEVES 


303 


occur,  not  at  regular  intervals,  but  in  groups,  separated  by  long 
pauses  (Fig.  133).  This  strange  effect  may  continue  for  two  or 
three  hours,  and  usually  exhibits  a  regular  course.  Often  the 
duration  both  of  the  groups  and  of  the  succeeding  pauses  declines 
regularly;  at  other  times  it  increases  in  the  primary  phase,  and 
declines  in  the  next :  other  cases  again  present  irregular  oscillations 
with  a  constant  tendency  to  decrease. 

The  number  of  beats  in  each  group  has  no  apparent  relation 
with  the  duration  of  the  respective  pauses.  Their  frequency  varies 
usually  in  regular  order. 

The  more  typical  groups  commence  with  rare  contractions  that 
are  gradually  accelerated,  and  then  again  slow  down  into  a  long 
pause.  The  height  of  the  contractions  in  each  group  usually 


FIG.  134. — Three  groups  of  beats  obtained  from  various  frogs'  hearts  tied  at  the  auricles. 
(Luciani.)  In  A  the  beats  form  a  descending  staircase  ;  in  B  they  are  approximately  the  same 
height ;  in  C  the  first  four  beats  form  aii  ascending  staircase. 

forms  a  descending  staircase ;  more  rarely  a  straight  horizontal 
line ;  more  rarely  still,  a  slightly  ascending  staircase  (Fig.  134). 

Our  experiments  tend  to  show  that  the  groups  are  of  longer 
duration,  and  the  intervals  between  them  shorter,  when  the 
ligature  is  nearer  the  sinus.  This  fact  agrees  with  Eckhard's 
conclusions — to  the  effect  that  the  duration  of  the  pause  increases 
in  proportion  as  the  incisions  in  the  heart  are  made  at  different 
heights,  from  limit  of  sinus  to  auriculo-ventricular  groove. 

The  periodic  rhythm  is  an  absolutely  constant  phenomenon 
when  the  cannula  is  attached  at  any  height  whatever  of  the 
auricles,  and  given  all  the  other  conditions  of  our  method,  in  re 
serum,  temperature,  and  pressure.  When  the  ligature  falls  on  the 
auriculo-ventricular  groove,  the  phenomenon  may  appear  in  a 
rudimentary  form,  or  may  be  altogether  absent.  When  it  falls  on 
the  upper  limit  of  the  ventricle  (1-1 '5  mm.  below  the  auriculo- 
ventricular  groove)  Bowditch's  preparation  is  obtained,  of  which  we 


304  PHYSIOLOGY  CHAP. 

shall  speak  below.  When  the  paroxysm  is  over  there  will  in  every 
case  be  some  isolated  contractions,  after  which  all  spontaneous 
movement  ceases,  although  the  ventricle  preserves  its  reflex' 
excitability,  and  responds  to  electrical  and  mechanical  stimuli  by 
strong  contractions.  When  the  ligature  falls  on  the  junction  of 
the  sinus,  the  periodic  grouping  of  the  cardiac  contractions  is 
barely  and  irregularly  indicated.  When,  lastly,  it  falls  on  the  sinus 
(1-1-5  mm.  above  its  opening  into  the  right  auricle)  no  trace  of 
periodic  grouping  is  visible. 

These  facts  obviously  exclude  the  hypothesis  that  the  periodic 
rhythm  observed  by  us  during  the  above  experimental  conditions 
depends  exclusively  on  a  specific  toxic  action  of  the  serum,  or  on 
asphyxia,  due  to  its  non- renewal,  as  was  held  by  Rossbach 
Langendorff  and  others ;  while  they  show  us  just  as  convincingly, 
that  in  the  case  of  our  experiments  the  fundamental  determining 
condition  of  the  phenomenon  consists  in  the  physiological  exclusion 
of  the  sinus  venosus  effected  by  the  ligature. 

They  further  show  that  the  rhythmical  activity  of  the  heart  is 


LHUILULUIL 


FIG.  135. —  Crisis  of  periodic  rhythm  in  frog's  heart  itied  3  mm.  above  the  auriculo- ventricular 
groove,  and  filled  with  pig's  serum.  (Luciani.)  Shows  gradual  dissolution' of  groups  into 
isolated  beats. 

most  highly  developed  in  the  venae  cavae  and  sinus  venosus 
(where  lie  the  conspicuous  ganglionic  masses  described  by  Eemak), 
after  the  separation  of  which  the  rhythmical  impulses  probably 
encounter  resistance,  and  must  summate  before  they  can  be 
efficacious.  Accordingly,  there  are  long  pauses,  during  which 
tension  is  accumulated,  and  groups  of  contractions,  during  which 
it  is  discharged  again. 

In  proportion  as  the  activity  of  the  heart  exhausts  itself  the 
pauses  shorten,  and  the  beats  in  the  groups  are  separated  by  wider 
intervals,  till  eventually  all  periodic  grouping  disappears.  This  is 
the  phenomenon  we  have  termed  the  "  crisis  "  (crisi),  represented 
by  a  longer  or  shorter  series  of  single  beats,  which  become  con- 
stantly rarer  and  weaker,  until  they  disappear  entirely,  as  soon  as 
the  asphyxia  and  exhaustion  of  the  heart  are  complete  (Fig.  135). 

The  crisis  indicates  that  the  resistances  which  determine  the 
periodic  rhythm  are  gradually  diminishing,  and  that  the  heart  is 
slowly  adapting  itself  to  the  new  conditions  produced  by  the 
ligature.  Eenewal  of  the  serum  after  the  crisis  has  set  in  does 
not  reinstate  the  periodic  rhythm.  This  is  a  striking  fact,  and  in 
our  opinion  indicates  that  the  adaptation  has  been  complete. 

IV.  At  the  time   at  which  we  took   up  these  physiological 


ix  CAKDIAC  MUSCLE  AND  NEEVES  305 

studies  of  the  frog's  heart  there  was  a  great  tendency  to  deny  any 
kind  of  automaticity,  and  to  regard  cardiac  rhythm  as  a  simple 
reflex  phenomenon  dependent  on  rhythmic  excitation  determined 
by  external  stimuli.  Goltz  assumed  that  systole,  by  removing  the 
cardiac  stimulus  (due  to  the  blood  and  its  gases),  induced  diastole. 
But  this  hypothesis  disregards  the  elementary  consideration  that 
the  excised  heart,  in  which  rhythmical  filling  and  emptying  is  no 
longer  possible,  continues  to  beat  vigorously. 

.  Others  ascribe  a  kind  of  elastic  resistance  to  the  heart,  alternat- 
ing with  the  different  phases  of  its  activity.  The  stimuli,  as 
continuous  agents,  must  develop  a  certain  tension  in  order  to 
surmount  this  elastic  resistance,  before  they  can  produce  their 
effect.  When  systole  is  over,  resistance  rises,  and  a  new  discharge 
can  only  take  place  after  the  latent  excitation  has  overcome  the 
corresponding  tension.  This  schematic  representation  implies  a 
tacit  recognition  that  the  immediate  cause  of  rhythmical  activity 
is  a  condition  intrinsic  to  the  organ.  But  the  naivett  of  this 
hypothesis,  which  predicated  a  kind  of  elastic  resistance,  was  shown 
on  the  discovery  of  periodic  rhythm,  which,  in  its  multiple 
manifestations,  its  varied  course,  and  its  crisis,  shows  how  change- 
able the  internal  conditions  which  determine  the  activity  of  the 
heart  may  be,  when  the  external  conditions  remain  constant  and 
almost  unaltered.  "  The  rhythm  of  the  heart-beats  "  (as  we  concluded 
in  1873)  "  is  the  external  expression  of  a  corresponding  rhythm  of 
the  nutritive  process  which  is  accomplished  within  the  organ." 

Henceforward,  no  one  contested  the  theory  of  the  automaticity 
of  cardiac  action,  since  it  was  impossible  to  invent  a  hypothesis 
which  explained  the  many  and  complex  forms  of  its  rhythm  by 
any  external  stimulus. 

The  automatic  excitability  of  the  heart  does  not  of  course 
exclude  its  reflex  excitability,  and  the  doctrine  of  Bidder  and 
Eckhard,  who  assumed  the  existence  of  distinct  automatic  and 
reflex  mechanisms,  must  be  modified  to  the  effect  that  the  different 
parts  of  the  heart  exhibit  different  degrees  of  excitability,  whether 
automatic  or  reflex. 

It  can  be  asserted  on  the  ground  of  weighty  arguments  that 
automatic  excitability  is  most  pronounced  in  the  venae  cavae  and 
sinus,  less  in  the  auricles,  and  least  in  the  ventricle.  The  facts 
already  cited  showing  that  (i.)  the  duration  of  cardiac  arrest,  after 
applying  ligatures  or  sections  to  the  heart  by  the  methods  of  Stannius 
and  Eckhard,  becomes  increasingly  greater,  the  lower  these  are 
placed  on  the  auricles  between  the  orifice  of  the  sinus  and  the 
auriculo- ventricular  groove ;  (ii.)  the  periodic  groups  become  con- 
stantly smaller  and  the  pauses  longer  with  physiological  separation, 
as  in  our  method,  combined  with  the  action  of  serum  and  of 
pressure  ;  (iii.)  the  arrest  of  cardiac  activity  by  exhaustion  due  to 
whatever  means,  which  takes  place  in  different  parts  of  the  organ 

VOL.  i  x 


306  PHYSIOLOGY  CHAP. 

at  different  times,  i.e.  first  in  the  ventricle,  then  in  the  auricles, 
lastly  in  the  sinus  and  the  venae  cavae, — all  go  to  prove  that 
automaticity  in  the  various  parts  of  the  heart  decreases  gradually  •' 
from  sinus  to  auricles,  from  auricles  to  ventricle.  To  these  facts, 
as  determined  on  the  heart  of  the  frog,  we  may  add  those  observed 
by  Mac  William  on  the  fish's  heart.  When  it  is  divided  into 
segments  each  of  these  continues  to  beat,  but  each  with  its  own 
proper  rhythm — the  more  slowly  in  proportion  as  the  segment  is 
farther  away  from  the  veins  opening  into  the  auricles. 

In  mammals,  again,  similar  phenomena  may  be  observed.  By 
an  ingenious  operative  method  Tigerstedt  succeeded  in  the  rabbit 
in  completely  separating  the  auricles  from  the  ventricles  without 
interrupting  the  circulation,  and  found  that  the  latter  continued 
to  beat,  although  the  rhythm  was  markedly  slower. 

Porter,  on  extending  the  experiments  with  artificial  perfusion 
through  the  coronary  system,  found  that  the  rhythm  persisted  even 
in  isolated  sections  of  the  ventricles  connected  with  the  rest  of 
the  heart  by  a  single  branch  of  the  coronary  artery. 

It  may  therefore,  generally  speaking,  be  concluded  that  every 

'-  segment  of  the  heart,  whether  in  poikilothermic  or  in  homothermic 

I'1  animals,  is  endowed  with  rhythmical  automatic  excitability,  which 

decreases  from  the  sinus  venosus  downwards,  from  the  mouths  of 

the  venae  cavae  to  the  auricles,  from  the  auricles  to  the  ventricles, 

Other  experiments  show  that  the  rhythmical  activity  of  the 
»|  more  automatic  determines  the  rhythm  of  the  less  automatic 
'  segments.  Gaskell  found  that  changes  of  temperature  localised  at 
the  sinus  in  the  frog's  heart  modified  the  frequency  of  the  beats  of 
the  whole  heart,  as  if  the  heart  had  been  warmed  or  cooled  in  toto. 
Adam  experimented  by  the  same  method  on  the  heart  of  cat  and 
rabbit.  He  saw  that  when  an  area  between  the  mouth  of  the  two 
venae  cavae  near  the  lowest  segment  of  the  wall  of  the  right 
auricle  was  warmed  or  cooled,  the  frequency  of  the  beats  of  the 
whole  heart  was  modified.  No  effect  was  produced  on  varying 
the  temperature  of  the  venae  cavae  or  pulmonary  veins,  of  the 
two  auricular  appendages,  or  the  walls  of  the  left  auricle.  It  is, 
'/  therefore,  evident  that  the  sinus  venosus  in  cold-blooded  animals 
and  the  orifice  of  the  venae  cavae  as  indicated  by  Adam  on  the 
mammalian  heart,  represent  the  most  automatic  parts,  in  which 
the  pulsatory  cycle  is  initiated,  and  on  which  the  frequency  of 
rhythm  of  the  entire  heart  depends. 

When  automatic  excitability  is  played  out,  reflex  excitability 
usually  persists  for  some  time  ;  when  the  heart  is  stimulated  either 
by  a  localised  mechanical  shock  or  by  an  induction  shock,  it  reacts 
with  a  beat  or  a  series  of  beats,  which  are  either  transmitted  to  the 
other  segments  of  the  heart,  or  remain  circumscribed  in  the 
segment  stimulated. 

When    reflex    excitability  is   extinguished,   the    reaction  to 


ix  CAEDIAC  MUSCLE  AND  BEEVES  307 

external  stimuli  ceases  in  the  various  segments,  in  the  same  order 
in  which  the  automatic  excitability  disappeared ;  first,  the  ventricle 
becomes  inexci table,  next  the  auricles,  and  shortly  after  the  sinus 
venosus.  On  the  basis  of  these  facts  it  may  be  sustained  that  the 
two  forms  of  excitability  are  in  direct  reciprocal  relation,  and  that 
the  segments  most  excitable  to  internal  stimuli  are  also  the  most 
excitable  to  external  stimuli. 

JVL_  Does  the  falling  excitability  (automatic  and  reflex)  from 
sinus  venosus  (or  mouth  of  venae  cavae)  to  auricles,  from  auricles 
to  ventricles,  which  determines  cardiac  rhythm,  depend  on  the 
varying  number  and  arrangement  of  the  ganglion  cells  in  the 
different  segments  of  the  heart,  since  these  have  the  property  of 
generating  rhythmical  impulses  which  are  then  transmitted  to  the 
muscle  cells,  provoking  contraction  in  the  form  of  a  peristaltic  wave  ; 
or  is  it  independent  of  the  intracardiac  nervous  elements,  and 
inherent  in  the  muscle  cells  of  the  myocardium  ?  For  a  long  time 
the  first  doctrine  was  very  generally  admitted.  Two  special 
phenomena  were  adduced  in  its  support  which  from  their  simplicity 
appeared  to  be  direct  evidence  : — 

(a)  The  lower  two-thirds  of  the  apex  of  the  frog's  ventricle, 

n  which  shows  no  nerve-cells  under  the  microscope,  invariably  ceases 

j\to  beat  automatically  when  separated  by  an  incision  or  ligature 

j  tfrom  the  other  parts  of  the  heart,  which  are  provided  with  nerve 

elements  (Stannard,  Eckhard  and  others).  *• 

(&)  Circumscribed  excitation  of  any  part  of  the  frog's  heart  and 
its  integuments  always  produces  a  contraction  that  commences  in 
the_auricles,  and  not  at  the  point  directly  stimulated  (Kiirschner, 
Budge,  Pagliani). 

The  first  phenomenon  seemed  to  be  a  direct  proof  of  the 
neurogenic  origin  of  automatic  excitability,  and  the  second  a  direct 
proof  of  the  neurogenic  origin  of  reflex  excitability.  Subsequently, 
however,  the  supposed  constancy  and  affirmative  character  of  both 
was  disputed. 

Eanvier  and  Engelmann  observed  rhythmical  pulsations  under 
the  microscope  in  fragments  of  the  adult  heart  in  which  it  was 
impossible  to  detect  any  trace  of  nervous  elements.  The  apex  of 
the  ventricle,  again,  when  excised  and  lightly  attached  to  a 
cannula  will,  after  a  pause  (if  conveniently  distended  and  irrigated 
with  a  nutrient  fluid),  begin  to  beat  spontaneously,  and  continue  to 
do  so  for  a  long  time,  although  the  rhythm  may  be  slower  than 
usual.  This  proves  that  even  if  this  part  has  no  ganglia,  it  also 
has  an  inherent  automatic  capacity,  although  to  a  much  smaller 
extent  than  the  rest  of  the  heart.  It  should  be  added  that  this 
masked  excitability  is  a  characteristic  peculiar  to  the  ventricle  of 
the  adult  frog.  That  of  the  tortoise,  on  the  contrary,  although  it 
has  no  nerve-cells,  will  beat  for  a  considerable  time  after  it  has 
been  isolated  (Gaskell). 


308 


PHYSIOLOGY 


CHAP. 


J 


Some  trustworthy  observers,  on  the  other  hand,  have  con- 
tradicted the  statements  of  Kiirschner,  Budge,  and  Pagliani,  and 
hold  that  the  reaction  of  the  heart  to  a  circumscribed  stimulus 
invariably  commences  in  the  part  directly  excited,  whence  it  is 
propagated  either  in  the  peristaltic  or  in  the  anti-peristaltic  form, 
i.e.  from  auricles  to  ventricle,  or  from  ventricle  to  auricles. 

On  the  theory  of  the  myogenic  origin  of  the  rhythmic  activity 
of  the  heart  in  all  animals,  both  in  the  embryonic  and  the  adult 
state,  this  rhythmicity  must  be  an  inherent  property  of  the  muscle 
cells,  independent  of  the  agency  of  the  nervous  system  (whether 
extra-  or  in tra- cardiac),  which  thus  fulfils  simply  a  secondary 
function,  regulatory  and  trophic.  Many  workers  have  contributed 
to  the  elaboration  and  stability  of  this  view,  among  them 
Engelmann  in  Germany  (1893-97),  Gaskell  in  England  (1882-87), 
and  Fano  in  Italy  (1885-90). 

Some  of  the  experimental  arguments  on  which  the  myogenic 
hypothesis  was  founded  have  been  disproved  by  more  recent 
investigations  carried  out  with  better  technical  methods,  which 
show  the  presence  of  nerve-cells  in  points  of  the  heart  at  which 
their  non-existence  had  previously  appeared  certain.  The  follow- 
ing arguments  of  the  myogenists,  however,  seem  incontestable : — 

(a)  The  automatic  movements  of  the  embryonic  heart  begin 
before  the  presence  of  ganglion  cells  can  be  demonstrated  under 
the  microscope.  In  the  chick,  for  instance,  the  heart  begins  to 
beat  thirty-six  hours  after  incubation,  while  the  ganglion  cells  are 
only,  formed  after  six  days  (His,  jun.) ;  the  human  heart  begins  to 
beat  three  weeks  after  gestation  (Pfliiger),  while  the  nervous 
elements  only  appear  at  the  commencement  of  the  fifth  week  (His, 
jun.).  The  ganglia  or  cardiac  nerves  are  not  formed  in  situ  by  the 
differentiation  of  the  muscle  cells  of  which  the  cardiac  tube  is 
composed,  but  enter  the  heart  from  outside,  from  the  cerebrospinal 
and  sympathetic  systems,  penetrating  along  the  veins  in  the  lower 
vertebrates  (fishes,  frogs),  along  the  arteries  in  the  higher  verte- 
brates (birds,  mammals) — (His  and  Eomberg). 

(&)  In  studying  the  cardiac  function  of  the  excised  embryonic 
heart  of  the  chick  on  the  second  or  third  day  of  development,  Fano 
succeeded  by  the  photographic  registration  of  its  movements  in 
demonstrating  that  the  beats  of  the  primitive  cardiac  tube  differ  in 
no  essentials  from  those  of  the  adult  heart.  It  exhibits  a  rhythm 
in  the  form  of  a  peristaltic  movement  that  passes  from  the  auricular 
to  the  ventricular  segment  of  the  tube.  The  first  portion  is  more 
resistant,  the  second  is  more  easily  exhausted.  If  divided  by  a 
transverse  section,  the  first  continues  to  beat,  the  second  stops. 
Longitudinal  or  oblique  sections  of  the  cardiac  tube  show  that  the 
segment  nearest  the  venous  end  is  the  first  to  contract,  and  from 
it  the  contractile  wave  is  propagated  towards  the  arterial 
extremity.  Toxic  or  indifferent  gases  first  arrest  the  beats  of 


IX 


CARDIAC  MUSCLE  AND  NEKVES 


309 


the  ventricular,  then  those  of  the  auricular  portion.  On  sub- 
stituting air  or  oxygen  for  the  said  gases,  shortly  after  the  beats 
have  been  arrested,  they  are  seen  to  reappear,  first  in  the  auricular, 
subsequently  in  the  ventricular  section.  In  short,  the  embryonic 
heart  of  the  chick,  which  has  no  nerve  elements,  exhibits  like  the 
adult  heart  a  decrease  of  automaticity  from  the  venous  to  the 
arterial  end  (Fig.  136). 

(c)  No  less  interesting  are  the  observations  of  Fano  in  regard 
to  the  mode  in  which  the  rhythm- 
ical   automatic    activity   of   the 

same  embryonic  heart  becomes 
exhausted.  When  isolated  and 
exposed  to  favourable  conditions 
of  moisture  and  temperature,  it 
continues  to  beat  for  a  time  which 
usually  exceeds  one  hour,  and 
may  reach  a  maximum  of  two  or 
three.  But  in  the  last  stage  o 
its  life,  rhythmical  is  transformed 
into  periodic  activity,  as  repre- 
sented by  groups  of  beats  separated 
by  long  pauses,  in  complete  agree- 
ment with  the  phenomenon  dis- 
covered by  us  on  the  adult  heart 
of  the  frog.  As  in  that,  so  in 
the  embryonic  heart,  the  periodic 
rhythm  gradually  resolves  itself 
into  an  irregular  series  of  single 
beats,  which  become  constantly 
weaker  and  less  frequent  until 
they  vanish  altogether.  The 
auricular  or  venous  segment  of 
the  heart  not  only  beats  a  good 
deal  longer  than  the  ventricular 
segment,  but  it  exhibits  the 
periodic  grouping  of  beats  much 
later.  After  the  automatic  rhythm 
ceases,  reflex  excitability  continues  for  some  time.  Since  these 
effects  appear  in  a  part  entirely  devoid  of  nervous  elements,  they 
can  only  be  due  to  automatic  or  reflex  excitability  of  the  embryonic 
muscle  cells. 

(d)  On  repeating  the  same  observations  and  experiments  on 
the  chick's  heart  in  the  second  half  of  its  development,  i.e.  on  the 
eleventh  day  of  incubation,  when  there  is  no  essential  morphological 
difference  between  it  and  the  adult  heart  of  vertebrates,  Bottazzi 
obtained  the  same  results  as  those  recorded  by  Fano  for  the  first 
hours  of  incubation.     In  that  stage  of  development  also  automaticity 


FIG.  l:U5.—  Chick's  heart  on  third  day  of  in- 
cubation. (Fano.)  AD,  venous  extremity, 
from  which  the  auricles  develop ;  EC, 
arterial  end,  from  which  the  bulbi  arteriosi 
develop ;  EF,  median  line  of  ventricular 
portion  ;  AB,  concave  line,  or  lesser  curva- 
ture of  heart ;  DFC,  convex  line,  or  greater 
curvature  of  heart.  Each  of  the  divisions 
indicated  below  the  figure  corresponds  to 
0'05  mm.,  and  the  whole  line  to  1  mm. 


310  PHYSIOLOGY  CHAP. 

declines    from    sinus    to    auricles,    from    auricles    to    ventricles. 
Functional  exhaustion  is  again  preceded  by  the  phenomenon  of 
periodic  rhythm,  or  crisis,  similar  to  that  described  by  us  for  the  ' 
adult  frog's  heart. 

(e)  We  have  seen  that  it  is  possible  to  revive  the  rabbit's  heart 
five  days  after  death,  by  the  artificial  circulation  through  the 
coronary  arteries  of  suitable  nutrient  fluids,  at  a  given  temperature 
and  pressure  (Kuliabko).  Now  it  has  been  found  by  experiments 
on  the  vitality  of  the  peripheral  ganglionic  elements  in  general, 
that  they  survive  suppression  of  circulation  very  imperfectly  in 
comparison  with  the  conducting  nerve  fibres,  and  more  particularly 
with  the  muscle  cells.  Langendorff  demonstrated  loss  of  excitability 
in  the  ciliary  ganglion  immediately  after  bleeding  and  death  from 
asphyxia  of  an  animal,  and  showed  that  the  pre-ganglionic  fibres 
ceased  to  influence  the  pupil  long  before  the  post-ganglionic.  H. 
E.  Hering  confirmed  this  fact  (1903),  but  noted  that  the  excitability 
of  the  vagus,  and  still  more  of  the  sympathetic,  for  the  heart,  per- 
sisted for  a  considerable  time  "after  the  death  of  the  animal.  He 
further  observed  that  when  the  cells  of  the  superior  cervical 
ganglion  had  ceased  to  function  it  was  impossible  to  revive  it 
by  pel-fusion  with  Ringer's  solution,  which,  however,  can  restore 
vagus  excitability  six  hours  after  the  death  of  the  animal,  and 
that  of  the  accelerator  fibres  after  a  much  longer  period  (fifty- 
three  hours).  If,  now,  the  intracardiac  behave  like  the  other 
sympathetic  ganglia,  it  is  evident  that  the  rhythm  of  the  heart, 
which  may  be  re-established  by  Ringer's  solution  as  much  as  six 
days  after  death,  cannot  be  due  to  the  ganglia,  but  must  derive 
from  the  automatic  recovery  of  the  muscle  cells. 

The  absolute  and  unconditional  value  of  some  of  the  arguments 
for  the  myogenic  theory  of  cardiac  rhythm  is  challenged  by  the  work 
of  Bethe  (1903),  who  adopted  an  improved  technique,  based  on  the 
staining  of  nerve  elements  by  methylene  blue.  According  to  these 
observations  thexe_js  jiot  in  the  whole  body  of  the  frog  ajmuscle 
richer  in  nerve  fibres  than  the  heart.  A  fine  network  of  fibrils 
,  from  the  minutest  ganglion  cells  invests  the  muscular  sheath  of  the 
entire  myocardium,  including  the  apex  of  the  ventricle.  Bethe 
asserts  that  the  muscles  of  the  auricle  in  the  frog  are  completely 
separated  from  those  of  the  ventricle,  just  as  these  last  are 
separated  from  the  muscles  of  the  aortic  bulb.  The  nervous 
reticulum  of  the  auricles  again  does  not  seem  to  be  in  direct 
continuation  with  that  of  the  ventricle,  but  is  connected  with  it 
exclusively,  or  at  least  to  a  great  extent,  by  means  of  Bidder's 
ganglia,  which,  as  we  have  seen,  lie  in  the  auriculo-ventricular 
groove. 

On  these  histological  grounds,  Bethe  ranges  himself  among  the 
supporters  of  the  neurogenic  theory,  alleging  that  while  the  nervous 
reticulum  of  the  heart  is  not  the  sole  incentive  to  its  rhythmic 


ix  CAEDIAC  MUSCLE  AND  NERVES  311 

automatic! ty,  it  does  represent  the  conducting  element  of 
excitation. 

The  most  important  and  convincing  arguments  in  favour  of 
the  neurogenic  theory  of  cardiac  rhythm  were,  however,  adduced 
by  Carlson  (1904-5). 

He  directed  all  his  observations  to  the  invertebrate  heart,  in 
which,  from  the  phylogenetic  point  of  view,  the  automatic  activity 
of  the  muscle  cells  should  reach  their  highest  development. 

One  of  the  strongest  arguments  adduced  by  Engelmann  in 
favour  of  the  myogenic  theory,  was  the  non-existence  of  nerves 
and  ganglion  cells  in  the  adult  heart  of  many  of  the  Invertebrata 
(molluscs,  arthropods,  tunicates,  lower  crustaceans).  He  reasoned 
from  the  observations  of  A.  Brandt,  C.  Eckhard,  M.  Foster  and 
Dew  Smith,  W.  Biedermann  and  Ransom.  Carlson,  however, 
noticed  that  these  negative  results  do  not  hold  for  all  invertebrates. 
In  a  great  many  molluscs  and  arthropods  the  heart  is  visibly 
invested  with  nerve-cells  and  fibres,  while,  according  to  Hunter, 


FIG.  137.— Heart  and  cardiac  nerves  of  Limulus  polypJiemus.  "(Carlson.)  an,  Anterior  arteries  ;  la, 
lateral  arteries ;  In,  lateral  nerves ;  mnc,  median  ganglionic  chain ;  os,  ostii  or  afferent 
stomata,  each  pair  of  which  corresponds  to  one  of  the  segments  into  which  the  Limulus  heart 
is  divided. 

these  elements  also  exist  in  certain  tunicates,  e.g.  in  Molgula. 
Carlson  worked  on  the  heart  of  an  invertebrate,  Limulus 
polyphemus  (an  arachnid,  according  to  others  a  crustacean),  the 
American  "  horse-shoe  crab."  The  heart  of  this  animal  (which  in 
the  best-developed  specimens  may  be  as  much  as  10-15  cm.  long) 
is  in  the  form  of  an  elongated  sac,  divided  into  segments  by 
arterial  rami  which  originate  in  a  double  lateral  series  (Fig.  137). 
During  systole  this  heart  contracts  simultaneously  in  its  entire 
length,  or  else  the  wave  of  contraction  is  peristaltically  propagated 
with  such  velocity  that  the  eye  is  incapable  of  following  its  pro- 
gression. The  nerve  plexus  by  which  the  heart  is  invested  is 
disposed  above  the  ectocardium  in  three  principal  trunks,  the 
median  of  which  may  be  regarded  as  an  extended  nervous  ganglion, 
mixed  with  nerve  fibres,  while  the  two  lateral  nerves,  and  the 
branches  by  which  these  are  connected  with  the  median  ganglion, 
contain  no  nerve  fibres.  In  this  case,  therefore,  it  is  comparatively 
easy  to  separate  the  nervous  elements  without  injuring  the 
muscular  walls  of  the  heart,  which  is  impossible  in  any  other 
animal. 

By  a  technique  as   simple  as   it   is   conclusive,  Carlson  has 


312  PHYSIOLOGY  CHAP. 

shown  that  the  conduction  of  excitability  and  co-ordination  of  the 
cardiac  movements  of  Limulus  depend  on  the  median  ganglion 
cord.  When  this  is  removed  the  beats  cease  entirely,  while  the 
intact  heart,  when  exposed,  may  continue  to  beat  regularly  for 
many  hours.  On  dividing  the  cord  at  any  point,  the  beats  become 
a-synchronous  in  the  several  segments,  and  continue  so  for  an 
indefinite  time.  When,  on  the  other  hand,  the  muscle  is  divided 
transversely  at  any  point  along  the  heart,  while  the  ganglion  cord 
is  spared,  there  is  no  longer  any  appreciable  disturbance  of  co- 
ordination in  the  pulsations.  If  a  single  node  of  the  ganglion 
cord  is  extirpated,  the  heart  ceases  to  beat  in  the  corresponding 
muscular  segment,  while  it  continues  to  beat  in  the  rest. 

The  ganglion  cord  of  Limulus  is  the  centre  not  only  for  the 
automatic  activity  of  the  heart,  but  for  its  reflex  activity  as  well. 
It  receives  the  moderator  and  accelerator  nerves,  which  modify  the 
cardiac  beats  acting  not  directly  on  the  muscle  cells,  but  reflexly  or 
through  the  ganglion.  When  this  has  been  excised,  and  the  beats 
of  the  heart  have  ceased,  rhythmical  activity  is  not  restored  on 
exciting  the  lateral  nerves;  tetanic  contractions  are,  however, 
obtained. 

Lastly,  certain  cardiac  poisons  (atropine,  nicotine)  act  on  the 
Limulus  heart  as  on  that  of  vertebrates,  paralysing  the  activity  of 
the  inhibitory  nerve  fibres  which  reach  it  from  without. 

There  can  be  no  doubt  as  to  the  accuracy  of  Carlson's  experi- 
ments, or  the  theoretical  conclusions  which  result  from  them.  As 
the  supporters  of  the  myogenic  theory  emphasise  particularly  the 
automatic  rhythmical  activity  of  the  embryonic  heart  and  that  of 
certain  invertebrates  in  which  nervous  elements  are  wanting ;  so 
the  supporters  of  the  neurogenic  theory  may  invoke  the  Limulus 
heart  as  direct  evidence  and  proof  that  its  automatic  and  reflex 
excitability,  the  conduction  and  the  co-ordination  of  excitations, 
depend  exclusively  on  the  ganglion  cells  which  it  contains. 

Without  venturing  on  any  general  conclusion,  and  assuming 
that  the  results  obtained  from  Limulus  are  applicable  to  the  heart 
of  vertebrates  also,  it  is  only  fair  to  admit  unhesitatingly  that  the 
neurogenic  theory  seems  more  probable  since  Carlson's  discovery 
than  the  myogenic.  Its  definite  and  unconditional  acceptance  for 
the  heart  of  every  animal  could  only  be  possible  if,  with  better 
methods  of  research,  it  were  discovered  that  both  the  embryonic 
heart  of  mammals,  and  the  heart  of  all  invertebrates,  possess 
ganglionic  elements  that  have  so  far  evaded  detection. 

VL^The  elements  which  constitute  the  vertebrate  myocar- 
dium are^otTperfectly  comparable  with  those  of  either  striated 
or  smooth  muscle.  They  are  neither  composed  of  fibres,  nor  of 
fusiform  fibro-cells;  but  consist  of  nucleated  cells  of  prismatic 
form,  which  usually  bifurcate  into  two  broad  short  processes,  and 
exhibit  a  rather  dark  stria tion.  Each  cell  is  joined  at  its 


IX 


CAKDIAC  MUSCLE  AND  NERVES 


313 


extremity  to  other  similar  cells  by  means  of  little  protoplasmic 
bridges  (Przewoski),  and  a  series  of  such  cells  constitutes  a  cardiac 
fibre,  which  never  has  a  sarcolernma,  and  is  joined  by  the  processes, 
as  above,  to  other  adjacent  fibres,  making  with  them  a  kind  of 
network.  At  certain  points,  more  particularly  beneath  the 
endocardium,  are  muscle  cells  that  are  non-striated,  or  striated 
only  in  the  outer  layers,  with  no  striae  at  the  nucleus  (Purkinje). 
These  represent  cells  which  are  less  well  developed  and  more 
embryonic  in  char- 
acter (Fig.  138). 

Given  this  struc- 
ture of  the  ele- 
ments of  the  myo- 
cardium, it  is  easy 
on  the  myogenic 
theory  to  see  how 
the  contraction 
wave  which  arises  in 
the  more  automatic 
muscle  cells  of  the 
venae  cavae  and 
sinus  venosus  must 
be  propagated  in  a 
peristaltic  form 
from  cell  to  cell,  in- 
dependent .  of  the 
nervous  system. 
Each  cell  being  in 
simple  protoplasmic 
continuity  with  all 
the  rest,  the  entire 
myocardium  may, 
from  a  physiological 
point  of  view,  be 
regarded  as  a  united 
mass  of  hollow  muscle.  We  must  now  briefly  enumerate  the 
most  important  experimental  facts  by  which  this  theory  is 
supported. 

As  early  as  1874  A.  Fick  showed  that  any  excitation  due  to 
stimulation  of  a  circumscribed  area  of  the  cardiac  muscular  mass 
was  propagated  in  every  direction.  Engelmann  almost  simul- 
taneously confirmed  this  fact,  and  further  showed  that  the  con- 
traction can  be  propagated  in  a  ventricle  divided  into  zigzags  by 
incisions,  from  one  section  to  another. 

Porter  (1899)  established  a  similar  fact  for  the  heart  of 
mammals,  irrigated  with  defibrinated  blood  circulated  through  the 
coronary  arteries,  at  36°  C.  After  cutting  across  the  mass  of  the. 


FIG.  138. — Muscular  network  of  normal  heart  of  adult  man.  (Prze- 
woski.)  'a,  Terminal  granular  layer;  b,  filiform  protoplasmic 
processes,  stretched  between  the  muscle  cells  ;  c,  nuclei  of  these 
cells  ;  d,  bundle  of  primitive  muscle  fibrils. 


314  PHYSIOLOGY  CHAP. 

ventricle,  in  such  a  way  that  the  segments  above  and  below  were 
united  only  by  means  of  little  muscular  bridges  and  the  rami  of 
the  coronaries,  synchronous  contractions  were  found  to  persist 
throughout  the  ventricular  mass.  These  facts,  which  appeared 
incompatible  with  nervous  conduction,  have,  since  Bethe's  work 
on  the  neuro-ganglionic  system  diffused  throughout  the  frog's 
myocardium,  and  that  of  Berkley  on  the  mammalian  myocardium, 
lost  all  evidential  value,  since  they  can  be  explained  by  the 
conduction  of  excitation  through  the  fibrillary  nervous  network. 

Gaskell,  to  exclude  the  intervention  of  nerves  and  ganglia 
in  the  transmission  of  cardiac  excitation,  divided  on  the  tortoise 
the  large  nerve  trunks  that  supply  the  ventricle,  and  on  the  frog 
excised  the  interauricular  septum  with  all  its  nerve  trunks,  and 
found  that  the  peristaltic  propagation  of  beats  from  auricle  to 
ventricle  was  not  interrupted.  Analogous  experiments  with  the 
same  results  were  carried  out  at  a  later  time  on  the  mammalian 
heart  by  Krehl,  in  collaboration  with  Kornberg.  These  experi- 
ments, however,  cannot  be  adduced  in  favour  of  the  theory  of 
myogenic  conduction,  since  it  has  been  demonstrated  by  the 
latest  histological  methods  that  the  whole  myocardium  is  pervaded 
by  minute  ganglionic  elements  and  nerve  fibrils. 

Either  on  the  hypothesis  of  rnyogenic,  or  on  that  of  neurogenic 
conduction,  it  is  difficult  to  explain  the  fact  of  the  brief  arrests 
or  delayed  transmission  of  the  contraction  wave  at  the  points  at 
which  it  passes  from  one  segment  to  the  other  of  the  heart,  i.e.  at 
the  junction  between  the  sinus  and  the  auricles,  the  auricles  and 
ventricle,  the  ventricle  and  the  arterial  bulb. 

It  was  formerly  assumed,  on  the  strength  of  the  early 
anatomical  researches,  that  each  of  these  parts  of  the  heart 
possessed  a  perfectly  distinct  system  of  muscle  fibres.  For  the 
heart  of  man  and  other  mammals,  in  particular,  Bonders  admitted 
as  a  well-established  fact  that  there  was  complete  interruption 
of  the  muscular  walls  corresponding  with  the  auriculo-ventricular 
groove,  and  he  used  this  to  account,  on  the  neurogenic  theory,  for 
the  perfect  a-synchronism  between  the  systole  of  the  auricles  and 
that  of  the  ventricles.  More  recent  and  exact  observations  have 
proved  the  existence  of  muscle  bridges,  which  connect  the  different 
parts  of  the  heart,  and  form  a  united  myocardium. 

As  early  as  the  end  of  1876  Paladinb,  in  the  heart  of  man  and 
various  other  vertebrates,  demonstrated  the  presence  of  muscular 
fasciculi  extending  uninterruptedly  from  auricles  to  ventricles.  In 
1883,  Gaskell  demonstrated  the  same  for  the  hearts  of  frog  and 
tortoise,  and  these  observations  were  subsequently  confirmed  by 
Stanley- Kent  (1892-94),  by  His,  jun.,  and  by  Engelmann,  for  the 
heart  of  other  vertebrates  also. 

According  to  the  recent  and  very  minute  researches  of  Tawara 
(1905)  on  the  human  heart,  this  connecting  system  of  auriculo- 


ix  CARDIAC  MUSCLE  AND  NERVES  315 

ventricular  fibres  forms  a  diffuse  and  complex  muscular  ramifica- 
tion, which  continues  uninterruptedly  from  auricles  to  ventricles. 
From  this  system  a  short  bundle  of  muscle  goes  out  at  the  back  to 
the  coronary  sinus,  where  it  joins  the  ordinary  muscles  of  the 
auricle.  Another  bundle  runs  inwards  from  the  muscular  system, 
towards  the  muscles  of  the  ventricle,  and  bifurcates  at  the  two 
walls  of  the  septum.  At  the  base  these  two  branches  break  up 
into  a  number  of  small  bundles,  some  of  which  enter  the  musculi 
•papillari,  while  others  spread  over  the  whole  internal  surface  of 
the  endocardium,  passing  either  to  the  apex  or  the  base  of  the 
ventricles.  Throughout  its  course  the  auriculo-ventricular  bundle 
is  separated  by  connective  tissues  from  the  cardiac  muscle  proper, 
and  connects  with  the  fibres  of  the  ventricle  by  its  terminal 
branches  only. 

It  would  be  interesting  to  study  the  effects  on  cardiac  rhythm 
of  interrupting  the 
conduction  of  ex- 
citation along  this 
system  of  muscle 
fibres,  which  passes 
uninterruptedly 
from  auricles  to 
ventricles.  Some 
physiologists  have 

tne  6X-  isolated  dog's  heart.     At  I  a  thread  was  tied  round  the  bundle  of 

OT1      the  ^s>  al^er  which  a  decided  allorhythmia  of  the  two  cardiac  seg- 

.     .  ments  is  apparent.     (Humblet.) 

isolated  surviving 

heart  of  mammalia :  e.g.  His,  jun.,  Graupuer,  Erlanger,  and  especially 
H.  E.  Hering.  Gentle  compression  of  the  principal  bundles  increases 
the  interval  between  presystole  and  systole,  without  altering  their 
normal  sequence.  Stronger  compression  produces  the  allorhythmia, 
in  which  2,  3,  or  4  presystoles  correspond  with  a  single  systole 
(Fig.  139).  Marked  and  sudden  compression  when  the  cardiac  / 
rhythm  is  very  frequent  and  intense  may  produce  a  longer  or  •* 
shorter  arrest  in  systole,  after  which  the  ventricles  begin  to  beat 
with  a  rhythm  of  their  own,  independent  of  that  of  the  auricles. 
TKe  same  results  occur  when  the  conductivity  of  the  auriculo- 
ventricular  bundle  is  impaired  by  cooling,  while  the  excitability 
of  the  auricles  is  simultaneously  raised  by  warming. 

The  experiments  which  most  definitely  bring  out  the  im- 
portance of  this  bundle  as  the  bridge  across  which  the  wave  of 
contraction  passes  from  auricles  to  ventricles,  are  those  of  H.  E. 
Hering  (1905)  on  the  dog's  heart.  He  kills  the  animal,  and 
then  revives  the  heart  (without  isolating  it  from  the  body), 
perfusing  Ringer's  physiological  solution  from  the  aorta  through 
the  coronaries.  While  the  heart  is  still  motionless,  he  divides  the 
auriculo-ventricular  bundle  by  a  comparatively  small  incision  in 

1 


Fin.  139.— Tracing  of  beats  of  auricle  (A)  and  ventricle  (H)  of  small. 
attempted  tne  eX- 


316  PHYSIOLOGY  CHAP. 

the  septum  (across  the  right  auricle).  Each  time  the  incision  into 
the  bundle  of  His  is  complete  (as  can  subsequently  be  ascertained 
anatomically)  a  sharp  functional  dissociation  between  the  beats  of 
the  auricles  and  those  of  the  ventricles,  a  true  allorhythmia, 
appears  when  the  cardiac  cycle  recommences.  Hering  studied  this 
effect  on  ten  dogs'  hearts,  with  results  as  follows : — 

(a)  The  ventricles  beat  more  slowly  than  the  auricles  (Fig.  140). 

(b)  The  wave  of  contraction  is  neither  transmitted  from  the 
auricles  to  the  ventricles,  nor  vice  versa,  whether  it  be  spontaneous, 
or  determined  by  external  artificial  stimuli. 

•   (c)  Both  auricles  and  ventricles  possess  independent  automatic 
activity. 

From  these  experimental  data  Hering  deduces  a  new  argument 
in  favour  of  myogenic  conduction,  adopting  the  ideas  previously 


FIG.  140. — Tracing  of  beats  of  auricle  (A)  and  ventricle  (V)  in  a  dog's  heart,  in  which 
the  bundle  of  His  had  been  cut.     Time  in  seconds.     (H.  E.  Hering.) 

brought  forward  by  Gaskell  in  connection  with  the  amphibian 
heart. 

According  to  Gaskell,  communicating  fibres  between  the  sinus 
and  auricles,  and  the  auricles  and  ventricle,  present  certain 
morphological  peculiarities  in  which  they  approximate  to  embryonic 
cardiac  fibres.  These  less  differentiated  fibres,  which  in  arrange- 
ment and  structure  resemble  those  of  the  primitive  cardiac  sheath, 
have  also  from  the  physiological  point  of  view  preserved  a  more 
embryonic  character,  since  they  are  endowed  with  a  far  higher 
degree  of  automatism,  and  probably  (according  to  Gaskell)  conduct 
the  excitation  from  cell  to  cell  far  more  slowly.  This  is  sufficient 
to  explain  in  the  simplest  possible  manner,  why  the  contraction 
wave  arising  in  the  sinus  is  not  of  uniform  velocity,- but  is  delayed 
at  the  limits  of  the  several  segments,  breaking  up  into  contractions 
of  sinus,  auricles,  ventricle,  and  bulbus  arteriosus. 

The  highly  developed  automatic  excitability  of  the  muscle  cells 
of  the  venae  cavae  and  sinus  explains  why  these  parts  govern  the 
rhythm  of  all  the  remaining  segments  of  the  heart,  where  automatic 


ix  CAEDIAC  MUSCLE  AND  NERVES  317 

activity  is  slower  and  weaker.  Gaskell  observed  (as  above)  that 
with  localised  warming  of  the  sino- auricular  and  ventricular 
segments,  acceleration  of  cardiac  rhythm  resulted  in  the  first  case 
only.  He  therefore  concluded  that  when  the  heart  is  functioning 
as  a  whole,  the  rhythm  proper  to  the  less  automatic  segments 
remains  latent  under  normal  conditions,  and  that  the  more 
frequent  and  powerful  rhythm  of  the  more  automatic  segments 
governs  the  movements  of  the  entire  heart.  This  is  the  reason 
why  under  normal  conditions  the  contraction  wave  always  travels 
in  the  peristaltic  direction  from  sinus  to  auricles,  from  auricles  to 
ventricle,  from  ventricle  to  bulbus  arteriosus. 

With  this  view  we  must  again  contrast  the  latest  results  of 
microscopic  work,  both  on  the  frog's  heart  (Bethe),  and  on  the 
muscular  bundle  of  His  in  the  mammalian  heart,  where  there  is 
found  to  be  an  exceptional  abundance  of  nerve  elements  (Hofmann). 

H.  E.  Heriiig  has  recently  (1907)  modified  his  previous 
opinions,  calling  attention  to  other  experimental  data,  which  he 
thinks  are  better  explained  on  the  neurogenic  theory.  These  are 
as  follows : — 

(a)  In  the  adult  mammalian  heart  there  is  a  segment  which, 
when  isolated  from  the  rest,  is  incapable  of  reacting  automatically. 
This   is   the  auricular  appendage  of  the  right  auricle.     It    now  / 
appears  from  microscopic  researches  that  this  particular  part  has 
no  ganglionic  nerve  elements. 

(6)  Under  certain  conditions  it  can  be  demonstrated  that  the 
automaticity  of  the  mammalian  heart,  and  its  capacity  for 
reacting  to  artificial  stimuli,  are  properties  independent  of  one 
another.  It  is  possible  for  a  heart  in  diastolic  or  systolic  arrest  to 
be  more  excitable  to  artificial  external,  than  to  automatic  internal 
stimuli,  and  vice  versa. 

(c)  A  small  incision  in  the  region  of  the  orifice  of  the  venae 
cavae,  or  a  single  induction  shock  of  minimum  intensity  in  the 
right  auricle,  may  suspend  the  automatism  of  the  auricular  region 
of  the  heart  for  a  considerable  period. 

(d)  Lastly,  Hering  has  recently  discovered  that  a  mammalian 
heart  arrested  from  any  cause  whatsoever,  is  capable  of  recom- 
mencing  its   beats   in   consequence    of   the    stimulation    of    the 
accelerator  nerve.     He  holds  that  these  facts  are  better  explained 
on  the  theory  of  a  nervous,  than  on  that  of  a  muscular  auto- 
maticity in  the  adult  mammalian  heart. 

VLL  It  can  be  demonstrated  independently  of  the  neurogenic 
or  inyogenic  theory  of  rhythm  that  cardiac  muscle  differs  from 
ordinary  skeletal  muscle  in  its  peculiar  physiological  characteristics. 
Bowditch  (1870)  was  the  first  to  study  in  Lud wig's  laboratory  the 
phenomena  exhibited  by  the  apex  of  the  heart  (attached  to  a 
simple  cannula  filled  with  serum,  and  connected  with  a  recording 
manometer),  when  excited  by  various  agencies. 


318  PHYSIOLOGY  CHAP. 

He  found  that  the  apex-beats  called  out  at  regular  intervals 
by  induction  shocks  did  not  increase  in  intensity  with  increased 
strength  of  stimulus,  as  is  the  case  with  normal  muscle.  When 
an  induction  current,  no  matter  of  what  intensity,  is  strong  enough 
to  provoke  a  contraction,  this  is  invariably  maximal,  i.e.  as  strong 
as  can  be  obtained  from  the  heart  at  the  given  moment  ("  all  or 
nothing,"  Law  of  Bowditch).  This  fact,  which  was  fully  confirmed 
by  the  observations  of  Luciani,  Kronecker,  and  Stirling,  proves  that 
the  contraction  of  cardiac  muscle  depends  essentially  upon  its 
inner  conditions,  and  to  a  much  less  degree  upon  the  external 
stimulus,  as  if  the  effect  of  the  latter  was  limited  to  enabling  the 
muscle  to  serve  up  a  spontaneous  contraction,  of  which  it  would 
not  have  been  capable  without  such  a  stimulus. 

This  view  is  justified  by  other  phenomena  elucidated  by 
Bowditch.  When  cardiac  muscle  is  stimulated  with  weak  in- 
duction shocks,  the  reaction  sometimes  occurs  and  sometimes  fails 
(stimolazioni  fallaci ).  If  the  strength  of  stimulus  is  increased,  or 
the  interval  between  each  is  diminished,  the  number  of  effective 


uiiiiiiuuiuiuii 


Fin.  141. — Bowditoh's  ascending  staircase  from  frog's  heart  ligatured  at  the  auricles,  with  a  series 
of  induction  shocks  thrown  in  at  intervals  of  4".  ,  (Luciani.)  The  tracing  shows  a  gradual  in- 
crease of  both  systolic  and  diastolic  excursions. 

shocks  increases  also.  If  the  current  is  still  further  strengthened, 
there  will  be  a  response  to  every  stimulus  (stimolazioni  infallibili}. 
After  a  long  series  of  regular  contractions  a  weaker  current  is  seen 
to  produce  the  same  effect.  Hence  a  strength  of  current  which 
js  at  first  uncertain  (fallace)  becomes  certain  (infallibile)  after 
/  P  a  sequence  of  shocks.  These  facts  prove  that  the  excitability 
of  cardiac  muscle  to  external  stimuli  is  very  variable,  and  oscillates 
from  one  moment  to  another,  and  that  the  contractions  are  capable  | 
of  determining  the  said  oscillations  of  excitability. 

On  experimenting  with  frogs'  hearts,  ligatured  at  the  auricles, 
we  obtained  the  same  results  with  Bowditch's  method  of  electrical 
stimulation  as  he  discovered  for  the  apex  of  the  heart. 

Another  phenomenon  that  can  be  observed  on  experimenting 
either  with  the  apex  or  the  auricular  ligature,  is  the  so-called 
Bowditch  staircase.  After  complete  rest  for  5  to  10  minutes, 
rhythmical  excitation  with  induction  shocks  of  uniform  strength, 
thrown  in  at  intervals  of  4  to  6  seconds,  produces  a  series  of 
contractions,  which  steadily  increase  in  height  up  to  a  certain 
maximum.  We  were  able  to  demonstrate  that  Bowditch's  stair- 
case expresses  not  merely  an  increment  in  systole,  but  an  increment 
in  diastole  also.  This  means  that  the  prolonged  rest  produces  a 


IX 


CAKDIAC  MUSCLE  AND  NEEYES 


319 


certain  inertia  in  the  heart,  associated  with  exaggeration  of  tonus, 
and  that  the  electrical  stimuli  arouse  the  heart  from  this  state, 
when  it  gradually  recovers  its  activity,  systolic  as  well  as  diastolic 
(Fig.  141). 

With  regard  to  the  tonicity  of  cardiac  muscle,  i.e.  the  inter- 
mediate state  between  systole  and  diastole,  at  the  pause,  Fano 
discovered  an  interesting  phenomenon  on  the  heart  of  the  tortoise 
(Emys  europea).  If  one  auricle  of  this  animal  is  connected  by  a 
thread  with  a  writing  lever,  its  spontaneous  beats  complete  them- 


FIG.  142. — A  and  13,  Myograms  from  auricle  of  tortoise  heart  (Emys  europea),  obtained  by  sus- 
pension method  ;  showing  two  different  .forms  of  rhythmical  oscillation  of  auricular  tone. 
(Fano.) 

selves  above  a  line  of  rhythmical  oscillating  tonicity.  These 
automatic  oscillations  of  tone  in  the  auricle  are  of  varying 
intensity,  and  comprise  a  larger  or  smaller  number  of  beats  (Fig. 
142,  A  and  B).  If  the  rhythm  of  the  two  auricles  is  recorded 
simultaneously,  it  will  be  seen  that  while  the  beats  are  perfectly 
synchronous,  the  oscillations  in  tone  of  the  two  auricles  are  quite 
independent  as  regards  intensity  and  frequency.  When  the  heart 
is  exhausted  the  oscillations  in  tone  are  the  first  to  disappear.  On 


/ 


C,  Oscillations  of  auricular  tone  in  toad's  heart  (Bufo  viridit)  (Bottazzi). 
D,  The  same  from  heart  of  Rana  esculeuta. 

exciting  the  vagi,  the  tonic  oscillations  increase,  while  the  beats 
are  arrested.  These  facts  led  Fano  to  suggest  that  the  rhythm  of 
tonicity  may  be  due  to  the  contraction  and  expansion  of  a  proto- 
plasmic substance,  other  than  that  which  determines  the  rhythm 
of  the  beats. 

Bottazzi  observed  automatic  oscillations  in  tonus  both  in  the 
auricles  of  the  amphibian  heart  (Fig,  142,  C  and  D)  and  also  on 
the  sinus  venosus,  even  when  they  were  bloodless.  Since  he  found 
the  same  phenomenon  in  the  oesophagus  of  amphibia  and  of  the 
chick  embryo,  and  Ducceschi  has  noted  it  in  the  stomach  of  the 
dog  (organs  which  consist  of  muscle  cells  that  are  very  rich  in 


320  PHYSIOLOGY  CHAP. 

sarcoplasm),  he  thinks  the  oscillations  in  tonicity  are  probably  due 
to  the  contractions  and  expansions  of  the  sarcoplasm,  and  the 
ordinary  and  more  frequent  beats  to  the  doubly  refractive  substance 
of  these  elements. 

The  oscillations  of  excitability  in  cardiac  muscle  recorded  by 
Bowditch  with  electrical  stimuli  were  determined  more  exactly  by 

the  later  work  of  Kro- 
necker  and    Stirling. 
They  showed  that  the 
heart  becomes  inexcit-  *T\ 
able  during  the  time     J 
of  its  contraction,  and    j 
that  if  cooled  this  in- J  / 
excitability      persists 
for   some    time   after 
the  beat  is  completed. 
These    facts   were 
confirmed   by  Marey, 
who      analysed      the 
phenomenon  of  peri- 
odic inexcitability  to 
electrical    stimuli    in 
the    automatically 
beating     heart,     and 
termed  it  the  refcac-    .'J 
tory     phase     of    the    ^ 
cardiac"  cycle.      It 
corresponds  with  the 
period  of  systole,  and 
its     duration     varies 

Fir;.  143.— MyOgrams  of  frog's  ventricle,  obtained  by  Marey  with  With       that       of        the 

apparatus  of  Fig.  126,  and  reduced  one-half  bv  photography.  afirrmli         anrl         ntV»oT 

Shows  effect  of  excitation  by  break  of  induction  current,  at  S™1111.       an°-      .  ®}™X 

various  moments  of  the  cardiac  cycle.     The  line  O  indicates  extrinSIC       Conditions. 

the    commencement    of   all   the    beats,  during  which    the  TTT-^I  i  j_-          i  • 

shock  is  sent  in.     In  1,  2,  and  3  the  heart  is  refractory  to  With      Weak       Stimuli 

the  stimulus.     From  4  to  8  the  heart  reacts  by  an  extra  i_"U0      vafvanfnrv     -rVhaeo 

systole,  by  a  delay  or  lost  time  which  is  progressivelyless,  l  .IdUlUl^     JJlld,St; 

assh~o\vn  by  the  sections  shaded  obliquely  to  make  them  more  riprsists  throughout 

conspicuous.     The  extra-systoles  increase  in  height  from  4  fl_^  &      ., , 

to  8,  each  being  followed  by  a  compensatory  pause.     At  ee,  the        Systole  :         With 
the  line  marked  by  the  electric  signal,  the  break  induction       ,    f  i-    •,     • 

shocks  were  thrown  in.  Stronger    Stimuli    it    IS 

limited    to    the    first    . 

period  of  systole,  or  obliterated  altogether.  Warming  shortens)/ 
or  suppresses  it ;  cooling  prolongs  it.  Each  forced  or  extra- 
sy stole  is  more  ample  in  proportion  as  iT^appears  later  after 
the  spontaneous  systole  that  preceded  it.  The_  extrasystole  is 
followed  by  a  resting  period  longer  than  that  which  usually  occurs 
between  two  syiMes^cprnpejasafe^ipause),  byjwhich  the  temporary 
disturbance  of  cardiac  rhythm  is  adjusted  (Fig.  143). 

Later  observers,  who,  after  Marey,  studied  the  compensatory 


ix  CAKDIAC  MUSCLE  AND  NEKVES  321 

pause  which  succeeds  the  extrasystole,  attributed  it  to  the 
intrinsic  nervous  system  of  the  heart,  because  in  experiments  with, 
the  apex,  where  there  were  supposed  to  be  no  ganglia,  the  extra- 
systole  appeared,  but  not  the  compensatory  pause  observed  upon 
the  intact  heart  supplied  with  ganglia  (Dastre,  Marcacci,  Gley, 
Keiser).  Subsequently,  however,  Engelmann  showed  that  the 
compensatory  pause  can  be  obtained  at  the  apex  also,  previous 
observers  having  failed  to  detect  it  because  they  employed  a 
tetanising  current  as  stimulus,  instead  of  single  make  or  break 
shocks.  He  demonstrated  that  the  compensatory  pause  may  fail 
in  the  entire  ventricle  also,  with  the  constant  current.  Bottazzi, 
on  the  other  hand,  observed  the  compensatory  pause  on  the 
embryonic  heart  of  the  chick,  which  excluded  the  possibility  of  its 
being  essentially  conditioned  by  the  nervous  elements. 

It  has  frequently  been  noted,  on  stimulating  the  heart  at  the 
sino-auricular  junction,  that  not  only  is  it  possible  to  obtain  an 
extrasystole  with  weak  currents  that  would  be  ineffectual  beyond  ^/ 
these  limits,  but  that  a  series  of  rhythmical  beats,  of  greater 
frequency  than  the  normal,  may  also  occur  (Langendorff,  Keiser). 
This  was  explained  by  the  presence  of  ganglion  cells  in  these 
parts.  But  in  view  of  Gaskell's  discovery  that  it  is  just  these 
parts  which  contain  the  more  embryonic  muscle  cells,  endowed 
with  a  marked  automatic  rhythm,  the  difference  observed  in  the 
response  may  obviously  depend  rather  upon  these  muscular 
elements  than  upon  the  ganglia. 

The  refractory  phase  of  the  cardiac  cycle  accounts  for  the 
regular  alternation  of  systole  and  diastole,  and  explains  why  it  is 
difficult  to  produce  a  true  tetanus  of  the  heart  by  means  of  a  / 
tetanising  current,  i.e.  to  fuse  a  number  of  contractions  into  a 
single  very  marked  and  persistent  one,  as  in  the  case  of  ordinary 
muscle  (Kronecker  and  Stirling). 

The  direct  action  of  tetanising  currents  upon  the  surface  of  the  / 
mammalian  heart  produces  the  strange  effect  termed  by  Ludwig  N 
and  Hoffa  (1849)  delirium  cordis.  This  is  a  wholly  unco-ordinated 
activity  of  cardiac  muscle,  in  which  it  contracts  at  isolated  points, 
and  simultaneously  relaxes  at  others,  so  that  the  mechanical  work 
of  the  heart  becomes  impossible.  Co-ordinated  activity  may  be 
resumed  after  a  delirium  lasting  for  several  minutes,  but  only 
when  the  current  has  not  been  unduly  strong,  nor  the  stimulation 
too  prolonged.  The  origin  of  this  phenomenon  has  been  variously 
explained.  MacWilliam  held  it  to  be  independent  of  nervous 
influences,  and  merely  the  effect  of  direct  excitation  and  altered 
conduction  in  the  muscle  cells.  Kronecker,  on  the  contrary,  inter- 
prets delirium  cordis  as  the  functional  disturbance  of  a  nervous 
centre  of  co-ordination  for  cardiac  movements,  situated  in  the 
upper  third  of  the  inter  ventricular  septum.  He  showed  that  in 
the  dog,  and  frequently  in  the  rabbit  also,  it  was  only  necessary 

VOL.  I  Y 


322  PHYSIOLOGY  CHAP. 

to  thrust  a  needle  into  this  spot  in  order  to  produce  a  fatal 
delirium  of  the  heart,  while  any  number  of  punctures  at  other 
points  of  the  ventricle  had  no  effect  on  the  co-ordinated  contrac- 
tions. The  trend  of  recent  evidence  in  favour  of  the  neurogenic 
theory  (which  has  always  been  upheld  by  Kronecker  for  the  heart 
of  mammalia  also)  increases  the  presumption  for  this  interesting 
hypothesis-  of  a  co-ordinating,  ganglionic  centre  for  cardiac  rhythm. 

VIII.  Admitting  that  the  rhythmicity  of  the  heart  depends 
on  the  automatic  and  reflex  excitability  of  its  intrinsic  ganglion 
system,  it  follows  by  exclusion  that  the  extracardiac  nerve  plexus 
through  which  the  heart  is  brought  into  relation  with  the  cerebro- 
spinal  axis  can  merely  exert  a  regulatory  function  upon  the 
rhythm,  modifying  it  in  accordance  with  varying  external 
circumstances  and  the  temporary  needs  of  the  body.  We  must 
now  investigate  the  nature  of  this  regulation  of  cardiac  movements 
as  exercised  by  the  nervous  system. 

At  the  Congress  of  Italian  Naturalists  at  Naples  (September 


FIG.  144.— Inhibitory  effect  of  electrical  excitation  of  frog's  vagus.    (Waller.)    Thp  pa 


lation  is  marked  on  the  abscissa  by  an  electric  siimal.     At  the  close  of  excitation  the  beats 
become  larger. 

1845)  the  brothers  Weber  communicated  the  results  of  certain 
experiments  which  they  had  undertaken  on  the  effect  of  stimulating 
the  vagus  by  tetanising  induction  currents.  To  their  surprise 
they  obtained  neither  acceleration  nor  reinforcement  of  the  beats 
>/  of  the  heart,  but  found  they  were  slowed,  or  arrested  in_diaatole. 
Stimulation  of  the  intact  vagus  or  its  peripheral  trunk  produced 
the  same  result  in  all  classes  of  vertebrates  (Fig.  144).  In  the 
frog  the  excitation  of  the  nerve  centres  from  the  optic  lobes  to  the 
tip  of  the  calamus  scriptorius  had  the  same  effect.  This  was  a 
discovery  of  capital  importance,  which  cleared  the  way  for  a  vast 
number  of  other  observations.  Budge  discovered  the  same  facts, 
independent  of  the  Webers,  and  almost  at  the  same  moment,  but 
declared  himself  unable  to  decide  whether  the  arrest  of  the  heart 
was  due  to  a  cardiac  tetanus,  as  he  was  then  inclined  to  believe, 
or  to  a  temporary  paralysis  of  the  heart  (for  which  he  subsequently 
concluded  on  becoming  acquainted  with  the  Webers'  communica-§ 
tion). 

Three  different  views  have  been  advanced  in  explanation  of  this 
phenomenon  :  that  of  the  Webers,  who  regarded  the  vagus  nerves 
as  the  restrainers  of  the  heart ;  that  of  Budge,  which  was  imme- 
diately accepted  by  Schiff  and  at  a  lator  time  by  Moleschott,  to  the 


IX 


CARDIAC  MUSCLE  AND  NERVES 


323 


effect  that  the  vagi  were  motor  nerves,  easily  exhausted  by 
electrical  stimuli ;  and,  lastly,  that  of  Brown-Sequard,  who  held 
the  vagus  to  be  a  vasomotor  nerve  of  the  coronary  system. 
Budge's  view  was  soon  found  to  be  untenable,  since  even  the 
weakest  currents  retard  or  arrest  the  movements  of  the  heart. 
Still  easier  was  it  to  overthrow  Brown-Sequard's  hypothesis,  seeing 
that  ligation  of  the  coronary  arteries  does  not  arrest  the  heart, 
and  in  the  frog's  heart,  which  has  110  cardiac  vessels,  the  vagus 
still  produces  the  same  effect.  Only  the  Webers'  theory,  therefore, 
remains,  and  the  object  of  later  researches  has  merely  been  to 
determine  the  mode  and 
mechanism  by  which  the 
retardation  or  inhibition 
of  the  beats  is  effected  in 
vagus  stimulation..  The 
most  important  results  of 
these  observations  are 
briefly  stated  as  follows:— 

In  warm-blooded  ani- 
mals the  standstill  brought 
about  by  the  vagus  never 
lasts  more  than  a  minute. 
If  the  curve  of  arterial 
pressure  is  registered  dur- 
ing vagus  excitation  by 
Ludwig's  kymograph,  a 
more  or  less  rapid  depres- 
sion may  be  observed, 
according  as  arrest  (Fig. 
145),  or  merely  slowing 
of  the  beats  (Fig.  146),  is 
obtained.  The  inhibitory 
action  is  more  pronounced 
in  mammals  than  in  birds, 
where  as  a  rule  there  is  only  delay  (Claude  Bernard),  or  arrest 
of  a  few  seconds  (Wagner,  Meyer).  In  the  poikilo thermic  verte- 
brates, on  the  other  hand,  the  standstill  is  more  pronounced  than 
in  mammals. 

Cardiac  arrest  by  vagus  stimulation  has  repeatedly  been 
determined  on  man.  Henle  obtained  it  in  1852  on  a  decapitated 
criminal,  whose  right  auricle  was  still  beating  (ultima  moriens) ; 
Czermak,  Thanhoffer,  Concato,  Malerba,  Wasilewsky,  Cardarelli 
obtained  it  by  compression  or  friction  of  the  neck  along  the  course 
of  the  vagus  and  the  carotids.  This  is  an  experimentum  peri- 
culosum,  since  it  may  produce  disquieting  systems  of  syncope 
(Thanhoffer). 

The  latent  period  of  vagus  excitation  is  comparatively  long, 


FIG.  145. — Depressor  effect  of  strong  excitation  of  vagus 
in  dog.  (Morat.)  The  period  of  stimulation  is  marked 
at  E  on  the  abscissa.  The  carotid  is  connected  with 
Ludwig's  kymograph. 


324  PHYSIOLOGY  CHAP. 

the  effect  being  usually  manifested  only  after  a  heart-beat  (Schiff, 
Pfliiger  and  others),  as  shown  in  Figs.  144,  145,  146. 

Excitation  by  a  single  induction  shock  has  little  effect ;- 
constant  currents  usually  produce  retardation  only;  tetanising 
induction  currents  are  the  most  effective  (Bonders,  Heidenhain, 
etc.). 

Stronger  currents  produce  a  more  obvious  and  prolonged  in- 
hibition ;  minimal  currents  always  produce  delay,  never  accelera- 
tion of  rhythm,  contrary  to  the  observations  of  Moleschott  (v. 
Bezold,  Pfliiger,  Rosen  thai,  etc.).  The  frequency  of  the  induction 


FIG.  140.— Depresaor  effect  of  moderate  excitation  of  frog's  vagus.    (Tigerstedt.)   The  two  vertical 
lines  indicate  the  duration  of  stimulation.     Carotid  connected  with  Lud wig's  kymograph. 

shock  tells  more  than  intensity  of  the  stimulus  (Legros  and 
Onimus). 

A  difference  in  the  inhibitory  action  of  the  two  vagi  has  often 
been  observed,  particularly  in  amphibia  (Meyer,  Gaskell,  Mac- 
William,  Wesley  Mills,  Tarchanoff).  In  the  rabbit  the  right 
vagus  is  often  more  effective  than  the  left  (Masoin).  The  same 
has  been  found  in  the  horse  and  dog  (Arloing  and  Tripier),  and 
also  in  man  (Czerrnak). 

When  on  cessation  of  the  arrest  produced  by  the  stimulation 
of  one  vagus  the  other  is  at  once  excited,  an  effect  similar  to  the 
first  is  produced,  without  any  resting  period,  if  the  first  nerve  had 
not  been  unduly  fatigued  (Tarchanoff,  Eckhard,  Mac  William  and 
others). 


IX 


CARDIAC  MUSCLE  AND  NERVES 


325 


Besides  the  modifications  of  rhythm  (Engelniaim's  chronotropic 

effects)  it   is   important    to   consider    the   changes   produced    by 

vagus  excitation  on  the  amplitude  of  the  beats,  or  more  exactly, 

on    the   degree   of   systolic   contraction    and    diastolic  expansion 

(inotropic  effect). 

Coats  was  the  first  (1869).  to  note  that  the  excitation  of  the 
[vagus  obstructed  systole 
land    favoured    diastole. 

He  found   by  exact   ob- 

servations, carried  out  in 

Ludwig's   laboratory   on 

the  frog's  heart  in  situ, 

connected  with  a  record- 

ing     manometer,     that 

vagus  stimulation,  with- 

out   moderating     the 

ble  suspension.  (Gaskell.) 
vagus   in  section  between 


Fin.  L47i— Myographic  tracing  of  frog's  heart :  A,  Auricles, 
,  ventricle,  with  method  of  double  sus{ 


Electrical  excitation  of   tlu 

the  two  vertical  lines.  Shows  arrest  of  beats,  both  in 
auricle  and  ventricle,  which  continues  after  the  close  of 
stimulation  ;  the  beats  subsequently  recommence,  and 
become  rapidly  larger  than  they  were  before  stimu- 
lation. 


not  iiifrpnnpntl 
11UL1I  ntl) 

diminished  systolic  con- 
*  traction  and  augmented 
the  diastolic  expansion. 
It  was  on  these  and  other 
phenomena  observed  in  the  dog,  in  relation  to  the  aspiration  of 
the  heart,  which  increases  during  vagus  excitation,  that  we  in 
1871  based  the  first  principles  of  our  theory  of  active  diastole  (see 
Chap.  VII.  8). 

Coats's  results  were  fully  confirmed  and  better  worked  out  in 
1882  by  Heidenhain  and  Gaskell.     The  former  found,  on  stimu- 


FIG.  148. — Myographic  tracing  of  frog's  heart  as  in  preceding  figure.    (Gaskell.)    In  this  case,  vagus 
stimulation  does  not  arrest  the  beats,  nor  retard  them,  but  diminishes  their  amplitude. 

lating  the  vagus  with  induction  shocks  thrown  in  at  intervals  of 
two  to  five  seconds,  that  the  systoles  -almost  disappeared  without 
diminishing  in  frequency. 

Gaskell  found  that  vagus  arrest  only  occurs  in  the  frog  when 
the  heart  is  well  nourished,  and  fails  to  come  off  when  it  is  slightly 
fatigued.  Figs.  147  and  148  represent  two  curves  obtained  by 


326  PHYSIOLOGY  CHAP. 

Gaskell,  from  the  frog's  heart,  in  which  the  inotropic  negative 
effects  of  vagus  stimulation  on  the  auricles  and  the  ventricle  are 
simultaneously  recorded.  The  greater  diastolic  relaxation  pro- 
duced by  the  vagus  is  not  necessarily  associated  with  diminished 
frequency  and  height  of  systole,  since  it  occurs  also  when  vagus 
stimulation  produces  no  change  either  in  frequency  or  intensity  of 
the  contractions.  This  fact,  which  has  been  substantially  con- 
firmed for  mammalia  by  the  researches  of  Mac  William,  Johannson 
and  Tigerstedt,  Franrois-Franck,  and  especially  by  Stefani  (Chap. 
VII.  8)  completely  justifies  us  in  applying  the  term  of  diastolic 
nerves  to  the  vagi.  We  shall  presently  consider  the  nature  of  the 
process  by  which  the  vagus  actively  incites  the  cardiac  diastole. 

In  addition  to  producing  negative  chronotropic  and  inotropic 
effects,  the  stimulation  of  the  vagus  can  also  impede  the  conduc- 
tion of  the  contraction  wave,  or,  in  Engelmann's  nomenclature,  can 
produce  negative  dromotropic  effects. 

NueT found  in  the  frog,  on  recording  the  contractions  of  the 
auricle  and  ventricle  separately,  by  means  of  writing  levers 
connected  to  those  parts  of  the  heart  by  threads,  that  vagus 
excitation  acts  more  easily  on  the  auricle  than  on  the  ventricle. 
Gaskell,  on  the  other  hand,  has  frequently  observed  the  opposite 
effect,  i.e.  that  the  ventricular  contractions  almost  disappeared, 
while  the  auricular  contractions  increased.  In  the  land  tortoise, 

(he  failed  to  establish  any  action  of  the  vagus  on  the  ventricle, 
while  the  contractions  of  the  auricles  were  much  reduced,  without 
any  slowing  of  rhythm.  Wesley  Mills  again  found  in  certain 
amphibia,  reptiles,  and  fishes  that  the  effect  of  the  vagus  was 
greater  on  the  auricles  than  on  the  ventricle ;  Mac  William,  how- 
ever, found  the  opposite  on  other  animals.  We  cannot  at  present 
give  any  explanation  of  these  phenomena. 

Other  facts,  on  the  contrary,  show  clearly  that  vagus  excitation 
diminishes  conduction  of  excitation  from  one  segment  of  the  heart 
to_a,agJilier.  Gaskell  noted  in  tortoises  that  stimulation  of  the 
right  vagus  had  no  effect  on  the  beats  of  the  sinus  venosus,  while 
it  brought  the  auricles  and  ventricle  to  a  complete  standstill.  In 
mammalia,  Mac  William  observed  cases  in  which  the  auricles  beat 
with  a  more  frequent  rhythm  than  the  ventricles ;  the  excitation 
was  not  propagated  from  the  first  to  the  second  segment,  although 
the  excitability  of  the  ventricles  was  undiminished.  Bayliss  and 
Starling  finally  discovered  a  method  by  which  it  is  easy  to  show 
that  the  stimulation  of  the  vagus  produces  negative  dromotropic 
effects.  They  induced  an  artificial  rhythm  of  the  heart  by  direct 
excitation  of  the  auricles  three  to  four  times  per  second,  and  then 
found  that  a  gentle  excitation  of  the  vagus  sufficed  to  reduce  the 
number  of  ventricle  beats  to  half  the  number  of  those  of  the 
auricle,  or  even  stopped  them  for  a  short  time,  while  the  auricle 
beats  continued. 


ix  CAKDIAC  MUSCLE  AND  NEKVES  327 

Some  observers  have  stated  that  during  the  arrest  of  cardiac 
movements  produced  by  vagus  stimulation  the  heart  becomes 
inexcitable  to  direct  artificial  stimuli  (Schiff,  Eckhard,  Mill). 
Mac  William,  on  the  other  hand,  observed  that  when,  in  mammals, 
vagus  excitation  produces  not  arrest,  but  pronounced  weakening 
of  the  systole  (negative  inotropic  effect),  the  value  of  the  threshold 
of  excitation,  or  least  minimal  efficacious  stimulus  applied  directly 
to  the  auricles,  rises,  i.e.  the  excitability  of  the  myocardium  is 
lessened.  Engelmann  found,  on  the  contrary,  in  the  frog's  heart 
that  during  the  inotropic  negative  effects  due  to  stimulation  of 
the  vagus,  excitability  of  the  auricles  to  direct  stimuli  may  remain 
unaltered,  and  even  sometimes  be  augmented,  which  he  terms  the 
positive  bathmotropic  effect.  Engelmann,  however,  admits  (experi- 
menting always  with  the  frog's  heart)  a  great  variety  in  the  results 
of  his  researches.  The  most  frequent  case  is  the  association  of 
negative  inotropic  with  negative  bathmotropic  effects  ;  but  other 
cases  are  to  hand  of  simultaneous  positive  bathmotropic  and 
positive  inotropic  effects.  At  other  times  vague  excitation  gives 
rise  now  to  inotropic  and  now  to  bathmotropic  actions. 

On  the  strength  of  this  last  fact  more  particularly,  Engelmann 
holds  that  the  changes  of  excitability  in  cardiac  muscle  (bathmo- 
tropic influence)  are  of  a  primary  nature  independent  of  the 
simultaneous  inotropic  influences.  This  opinion  is,  however, 
contradicted  by  H.  E.  Hering,  who  holds  the  bathrnotropic  effects 
to  be  secondary  and  dependent  on  changes  in  the  duration  of  the 
systole. 


DL^The  discovery  that  the  heart  receives  accelerator  or 
systolic  branches  of  the  sympathetic  in  addition  to  the  inhibitory 
or  diastolic  fibres  of  the  vagus  was  made  in  1862  by  V.  Bezold,  and 
worked  out  more  accurately  by  Bevor  (1866).  On  dividing  the 
two  vagi  and  cervical  sympathetics  in  rabbit,  excitation  of  the 
medulla  oblongata  and  cervical  cord  produced  a  rise  of  blood 
pressure,  with  acceleration  of  cardiac  rhythm.  On  repeating  the 
same  experiment  after  dividing  the  cord  between  the  first  and 
second  vertebra  (with  the  object  of  cutting  out  the  influence  of 
the  bulbar  vaso-motor  centre  of  Ludwig  and  Thiry),  acceleration 
was  obtained  without  rise  of  pressure.  There  must  accordingly  be 
accelerator  nerve  fibres  running  from  the  cervical  cord  through 
the  rami  communicantes  of  the  sympathetic  to  the  heart.  Yon 
Bezold  afterwards  demonstrated  that  these  accelerator  fibres  pass 
through  the  last  cervical  ganglion,  and  thence  to  the  heart. 

The  brothers  Cyon  obtained  the  same  results  in  1866,  on 
dividing  the  splanchnics  instead  of  the  cord  ;  and  further  observed 
that  when  the  first  thoracic  ganglion  was  destroyed,  there  was  no 
longer  acceleration  of  cardiac  rhythm. 

Schmiedeberg  (1870)  detected  the  presence  of  accelerator  fibres 
in  the  frog  also,  running  with  the  vagus  ;  after  a  mild  dose  of 


328 


PHYSIOLOGY 


CHAP. 


atropine  or  nicotine,  stimulation  of  these  nerves  no  longer  causes 

inhibition,  but  only  acceleration  of 

rhythm.      Heidenhain  (1882)  and 

Gaskell  (1884)  subsequently  showed 

that     the    accelerator    fibres     are 

derived  from  the  sympathetic,  and 

unite  with  the  latter  immediately 

after  the  vagus  leaves  the  cranium 

(Fig.  149). 

In    1871    Schniiedeberg,   with 
Ludwig,   studied    the    topography 


IX 


FIG.  149.— Left.  Diagram  of  frog's  cardiac  nerves.  (After,  Foster.)  fif,  Vagus  roots ;  PC,  cranial 
wall;  GV,  vagus  ganglion;  IX,  glosso-pharyngeal ;  VS,  vago-sympathetic ;  Sc,  cervical  sym- 
pathetic, which  unites  with  vagus  ganglion  ;  sc,  sympathetic  branch  which  traverses  the 
cranium  and  gives  off  fibres  to  the  Gasserian  ganglion  ;  Gci,  first  sympathetic  ganglion  receiv- 
ing fibres  from  first  spinal  nerve;  AV,  annulus  of  Vieussens  traversed  by  subelavian  artery; 
<rs,  second  sympathetic  ganglion  receiving  fibres  from  second  spinal  nerve ;  Gm,  third  sym- 
pathetic ganglion,  which  receives  fibres  from  third  spinal  nerves,  ;i°nr,  via  ramus  communicans, 
re.  The  direction  of  the  arrows  indicates  direction,  first  ascending,  then  descending,  in  which 
the  excitation  of  the  cardiac  fibres  by  the  vago-spinal  nerves  is  transmitted  to  the  heart. 

FIG.  150. — Right.  Diagram  of  cardiac  nerves  in  dog.  (After  Foster.)  The  upper  portion  of  the  figure 
represents  the  inhibitory  fibres,  the  lower  part  the  accelerators  ;  rV,  roots  of  vagus  ;  rS,  roots 
of  spinal  accessory,  the  internal  roots  of  which,  shown  by  black  line,  run  in  the  trunk  of  the 
vagus,  V  ;  GJ,  jugular  ganglion  ;  Gtv,  ganglion  of  vagus  trunk  ;  V,  trunk  of  vagus  united  with 
cervical  sympathetic  to  form  vago-sympathetic  nerve  ;  Sc,  cervical  sympathetic ;  Gci,  inferior 
cervical  ganglion ;  AV,  annulus  of  Vieussens  traversed  by  subclavian  artery ;  GS,  stellate  or 
first  thoracic  ganglion  ;  tic,  cardiac  nerves,  of  which  the  two  tipper  branches  come  from  the 
accessory  or  spinal,  and  the  two  lower  from  the  first  to  the  fifth  thoracic  nerves  (particularly 
from  second  and  third,  as  shown  by  black  lines),  the  fibres  of  which  ascend  by  rami  com- 
municantes  to  the  stellate  ganglion  and  from  the  loop  of  Vieussens.  The  direction  of  the'arrows 
indicates  the  direction,  first  ascending,  then  descending,  in  which  the  activity  of  the  cardiac 
nerves  travels  to  the  heart. 


of  the  cardiac  plexus  in  the  dog,  and  distinguished  the  inhibitory 
from  the  accelerator  fibres  (Fig.  150). 


ix  CARDIAC  MUSCLE  AND  NERVES  329 

The  inhibitory  fibres  arise  in  the  accessory  or  eleventh  cranial 
nerve.  After  extirpation  of  this  nerve  in  the  dog,  and  lapse 
of  .  sufficient  time  for  the  peripheral  fibres  running  with  the 
vagus  to  degenerate,  vagus  stimulation  produces  no  effect  upon  the 
heart,  as  was  shown  by  Waller  in  1S56,  and  subsequently  con- 
firmed by  Schiff,  Heidenhain,  and  Francois-Franck.  Giannuzzi, 
however,  found  that  vagus  excitation  still  produced  a  slight 
moderator  effect  fourteen  days  after  extirpation  of  the  accessory 
nerve,  which  he  ascribed  to  certain  fibres  belonging  to  the  vagus 
itself,  with  the  same  function  as  those  of  the  accessory. 

The  accelerator  fibres  unite  the  lower  cervical  with  the  first 
thoracic  (or  stellate)  ganglion.  They,  too,  emerge  from  the  cord 
(according  to  Strieker,  in  the  first  six  thoracic  nerves),  and  pass  by 
the  ranii  communicantes  to  the  sympathetic  system.  Albertoni 
and  Butalini  found  the  third  dorsal  nerve  particularly  effective 


Fio.  151. — Acceleration  of  heart-beats  by  brief  excitation  at  E  of  the  two  branches  of  the  nerve 
that  form  the  annulus  of  Vieussens,  in  curarised  ilog.  (l)oyon.)  Carotid  connected- with 
Ludwig's  kymograph. 

(Fig.  151).  The  cervical  trunk  of  the  vagus  also  seems  to  con- 
tain some  accelerator  fibres,  as  shown  by  the  action  of  atropin 
(Rutherford). 

The  functional  character  of  the  accelerator  fibres  was  studied 
by  Heidenhain  and  Gaskeli  on  poikilotherrnic,  and  by  Schmiede- 
berg,  Bowditch.  Baxt,  Boehm,  Fran^ois-Franck,  E.  Voit,  and  Roy 
and  Adaini  more  particularly  on  warm-blooded  animals.  Their 
results  may  be  summarised  as  follows : — 

Excitation  of  the  accelerators  manifests  itself  after  a  rather       s 
long  latent   period,    which   may   amount   to   two   seconds.     The    * 
maximum  of  acceleration  (positive  chronotropic  effect)  first  appears 
after  ten  or  more  seconds.     The  effect  of  a  brief  excitation  is 
therefore  shown  when  it  is  over,  as  an-  after-effect.     This  lasts  for 
a  considerable  time,  exceeding  two   •seconds.      The   duration    of 
acceleration  depends  on  the  length  of  stimulus,  since  the  accelera- 
tors are  hard  to  fatigue,  even  with  an  excitation  lasting  for  two 
minutes. 


330  PHYSIOLOGY  CHAP. 

The  acceleration  may  rise  from  7  per  cent  to  a  maximal 
70  per  cent,  according  to  the  prevailing  frequency  of  rhythm. 
The  difference  in  effect  depends  principally  on  the  frequency  of 
rhythm  previous  to  excitation.  The  maximum  of  acceleration  is 
not  increased  when  the  accelerators  on  both  sides  are  excited 
simultaneously.  The  duration  of  the  after-effect  is  in  proportion 
with  the  duration  of  the  stimulus. 

The  positive  inotropic  and  dromotropic  effects  must  be  dis- 
tinguished from  acceleration  or  positive  chronotropic  effects. 
Heidenhain  and  Gaskell  observed  on  the  frog  that  stimulation  of 
the  sympathetic  fibres  increases  the  height  of  systole  and  shortens 
diastole  by  raising  the  tonicity  of  cardiac  muscle  (inotropic  effect)  ; 
the  capacity  of  the  latter  to  transmit  the  excitation  from  one  segment 
to  the  next  (dromotropic  effect)  also  increases ;  the  effects  from 
every  point  of  view  are  antagonistic  to  those  of  the  vagus.  These 
facts  are  confirmed  in  essentials  by  thQ  investigation  carried  out 


Fie.  l'-2. — Augmentation  of  ventricle  beats  of  dog  after  electrical  tetanisation  of  first  left  acceler- 
ator nerve,  as  traced  on  abscissa.     (Franc.ois-Franck.) 

with  various  experimental  methods  on  mammals  by  Frangois- 
Franck,  Boy  and  Adami,  Bayliss  and  Starling.  They  appear  to 
justify  the  physiological  name  of  systolic  nerves  given  by  us  to 
the  cardiac  branches  of  the  sympathetic,  in  opposition  to  the 
diastolic  nerves  or  cardiac  fibres  of  the  vagus  (Fig.  152). 

When  these  two  nerves  (which  seem  to  be  antagonistic  in 
function)  are  excited  simultaneously,  the  effects  are  not  algebraic- 
ally  summed  up  and  cancelled,  but  both  are  expressed, — fir,&t-thoj>e 
propgr  to  the  vagus^-then^those^ from  the_syjmpajih^tic^  This 
remarkable  fact  was  discovered  on  the  dog"  by  Baxt  (1875)  in 
Ludwig's  laboratory.  It  can  also  be  observed  when  the  vagus  is 
excited  with  minimal  induction  currents,  and  the  sympathetic  with 
strong  currents  to  produce  maximal  effect  (Fig.  153).  The  probable 
interpretation,  according  to  Baxt,  is  that  the  two  kinds  of  nerve 
fibres  act  upon  the  heart  at  two  different  points.  During  the 
excitation  of  the  diastolic  nerve  the  fibres  of  the  systolic  nerve 
cannot  act,  the  excitability  of  the  cardiac  muscle  being  modified ; 
they  will  confine  themselves  to  storing  up  the  latent  excitability 
in  the  ganglion,  to  appear  as  an  after-effect  at  the  close  of 


IX 


CAEDIAC  MUSCLE  AND  NERVES 


331 


stimulation.  It  should,  however,  be  stated  that  the  experimental 
data  of  Baxt,  and  his  interpretation,  have  to  some  extent  been 
corrected  by  the  subsequent  work  of  Meltzer  (1897),  Reid  Hunt 
(189*7),  and  Engelmann  (1900) ;  who  demonstrated  that  the  effects 
consequent  on  the  simultaneous  stimulation  of  the  two  distinct 
cardiac  nerves  are  more  varied  and  complex  than  was  supposed  by 
Baxt,  and  that  the  chrono-  and  iso tropic  may  be  complicated  by 
dromotropic  effects. 

X.  After  defining  cardiac  inhibition  due  to  stimulation  of  the 
vagus  as  a  diastolic    effect,  in  so  far  as  it  favours  diastole  and 


FIG.  153.—  Diagram  representing  frequency  of  cardiac  beats  after  excitation  of  vagus  (continuous 
broarl  line),  accelerator  nerves  (continuous  thin  line),  and  of  both  nerves  (dotted  line). 
(Baxt.)  The  stimulation  of  the  accelerators  lasts  from  a  to  e,  (16"),  that  of  the  vagus  from  d 
to  e  (4"),  and  commences  12"  later.  Time  marked  in  seconds  on  the  abscissa  ;  number  of  beats 
occurring  in  each  2"  shown  on  areas  of  ordinates. 

obstructs  systole,  and  the  acceleration  due  to  the  sympathetic  as  a 
systolic  effect,  in-so  far  as  it  favours  systole  and  obstructs  diastole, 
we  still  have  no  definite  idea  of  the  inner  mechanism  of  these 
phenomena.  As,  according  to  the  supporters  of  the  myogenic 
doctrine,  the  automatic  rhythm  of  the  heart  is  a  property  inde- 
pendent of  the  nervous  system,  inherent  in  the  muscle  cells  of  the 
myocardium,  it  is  logical  to  assume  that  the  two  kinds  of  nerve 
which  influence  the  heart  from  without  determine  opposite  results, 
inasmuch  as  they  alter  the  metabolism  of  the  muscle  cells — which 
underlies  autoinaticity — in  an  opposite  direction.  This  was 
established  by  Gaskell  (1887)  in  his  important  discovery  of  the 


332  PHYSIOLOGY  CHAP. 

electrical  phenomena  that  accompany  the  inhibitory  processes, 
and  are  the  converse  of  those  concomitant  with  the  accelerator 
processes. 

The  intact  and  the  resting  heart  are  iso-electric.  When  any 
point  of  the  walls  is  injured,  or  excited,  by  any  cause,  that  point 
becomes  galvanometrically  negative  in  relation  to  the  intact,  or 
inacjdye,_parts :  and  on  connecting  the  injured,  or  active,  point 
with  any  other  intact,  or  inactive,  point,  a  current  known  as  the 
demarcation,  or  action,  current  passes  through  the  galvanometer 
(Hermann). 

Now  Gaskell  has  shown  that  if  the  heart  of  a  tortoise  is 
arrested  by  the  upper  Stannius  ligature,  and  the  tip,  of  the  auricle 
killed  with  hot  water,  then  on  leading  off  the  demarcation  current 
to  the  galvanometer,  and  exciting  one  of  the  branches  of  the  vagus 
(running  with  one  of  the  coronary  veins  from  the  sinus  venosus 
to  the  auriculo-ventricular  groove),  a  positive  variation,  i.e.  an 
increase  of  the  demarcation  current,  is  apparent.  Since  this  effect 
cauuot  be  due  to  increased  (galvanometric)  negativity  of  the 
dead  point,  we  must  assume  that  it  is  the  result  of  augmented 
(galvanometric)  positivity  of  the  intact  part.  We  must  therefore 
conclude  that  excitation  of  the  vagus  in  a  resting  heart  produces 
modifications  of  its  metabolism,  expressed  in  an  electrical  variation, 
opposed  to  that  which  occurs  in  the  contraction  of  cardiac  muscle. 

According  to  Gaskell,  the  altered  metabolism  produced  by 
vagus  excitation  consists  in  an  increase  of  reparatory  or  anabolic 
processes ;  while  the  stimulation  of  the  sympathetic  fibres  accelerates 
the  disintegrative  or  katdbolic  processes.  The  action  of  the  vagus 
is  therefore  diastolic  because  it  promotes  anabolic  processes,  while 
that  of  the  sympathetic  is  systolic  because  it  promotes  the  katabolic 
processes.  The  probability  of  this  theory  is  attested  by  the  fact 
that^  vagus  excitation  is  followed  by  a  phase  of  increased  activity 
as  its"  after-effect,  showing  that  the  cardiac  muscle  is  strengthened, 
not  weakened,  while,  on  the  other  hand,  excitation  of  the  sym- 
pathetic is  followed  by  breaking-down,  consumption,  and  exhaustion 
of  the  myocardium  (Gaskell).  The  anabolic  action  of  the  vagus 
'is,  as  we  have  seen,  associated  with  diminished  reflex  excitability 
of  the  cardiac  muscle  (negative  bathmotropic  effects),  so  that  the 
latter  on  direct  stimulation  no  longer  reacts  by  a  contraction,  save 
when  the  stimulus  is  excessive.  This  fact  explains  the  mechanism 
of  active  diastole,  as  determined  by  the  vagus ;  it  is  the  effect  of 
the  lowered  excitability  of  the  myocardium,  by  which  systole  is 
hindered,  and  diastolic  expansion  of  the  muscle  cells  promoted. 

Other  facts  described  at  different  times  by  various  authors 
harmonise  with  Gaskell's  theory  (which  Fano  was  the  first  to 
bring  forward  in  Italy).  Panum  and  Giannuzzi  observed  on  the 
rabbit  that  weak  stimulation  reinforced  a  previously  weakened 
cardiac  activity.  Traube  noticed  that  on  interruption  of  artificial 


ix  CAEDIAC  MUSCLE  AND  NEKVES  333 

respiration  in  curarised  animals,  the  heart  beat  longer  when  the 
vagi  were  intact  than  when  they  had  been  previously  divided. 
Brown-Sequard  found  on  bleeding  two  rabbits,  in  one  of  which  the 
vagus  had  previously  been  excited,  in  the  other  not,  that  asphyxia 
and  eventual  arrest  of  the  heart  were  produced  more  rapidly  in 
the  second  than  in  the  first.  Konow  and  Stenbeck  stated  that 
the  rabbit's  heart  in  situ,  but  completely  isolated  from  the  central 
nervous  system,  beat  for  a  shorter  time,  in  consequence  of  asphyxia, 
.than  when  the  vagi  were  left  intact  and  the  spinal  cord  destroyed. 

Lastly,  the  anabolic  action  of  the  vagus  was  confirmed  by  the 
nutritional  disturbances  that  occur  in  cardiac  muscle  some  time 
after  the  division  of  these  nerves.  Eichhorst  observed  in  birds, 
and  Wasilieff  in  rabbits,  that  the  division  of  the  vagi  resulted  in 
a  certain  degree  of  fatty  degeneration  of  the  myocardium.  The 
results  obtained  by  Fantino  and  Timofeew  were,  however,  more 
convincing.  The  former  confined  himself  to  cutting  one  vagus,  so 
that  the  operated  animal  remained  alive  for  a  longer  period. 
After  killing  this  animal  he  found  nothing  remarkable  at  the  post 
mortem,  except  the  atrophy  and  non-fatty  degeneration  of  the 
muscle  cells,  localised  in  various  regions,  according  as  the  right  or 
left  vagus  had  been  divided.  Timofeew  divided  the  right  vagus 
below  the  recurrens,  and  the  left  eight  days  later.  The  animal  only 
survived  the  second  operation  three  to  five  days.  Death  ensued 
from  adynamia  cordis,  owing  to  degeneration  of  the  cardiac 
muscle,  induced  by  the  failure  of  the  anabolic  action  of  the  vagus. 

The  value  of  these  positive  data  cannot  be  impaired  by  the 
negative  results  obtained  on  the  frog  by  Bidder  and  Klug,  since 
the  metabolism  of  these  animals  is  so  sluggish,  that  they  could 
survive  inanition  for  many  months. 

XL  We  must  next  investigate  the  processes  by  which  the 
systolic  and  diastolic  nerves  of  the  heart  regulate  the  cardiac 
rhythm.  It  has  long  been  known  that  the  heart  sends  information 
to  the  nerve  centres  of  all  modifications  in  its  functions,  but  the 
study  of  its  afferent  nerves  is  more  recent.  While  investigating 
the  physiological  function  of  the  different  branches  of  the  cardiac 
plexus  in  the  rabbit  (1886)  Ludwig  and  Cyon  discovered  a  branch, 
which  they  termed  the  depressor  nerve.  It  arises,  as  shown  in 
Fig.  154,  from  two  roots.  Its  division  produces  no  change  in 
cardiac  rhythm,  which  proves  that  it  is  not  in  tonic  excitation. 
Stimulation  of  its  peripheral  end  has  no  effect,  showing  that  it 
contains  no  fttfeqant  fibres.  Excitation  of  the  central  end  lowers 
arterial  blood  pressure,  and  simultaneously  retards  the  beats  of  the 
heart.  After  division  of  the  vagi  this  last  effect  is  abolished, 
while  the  first  remains.  The  slowing  of  the  rhythm  must  there- 
fore be  a  vagus  reflex,  and  the  arterial  depression  a  reflex  by  way  of 
the  vaso-dilators.  The  depression  of  blood  pressure  continues  after 
cutting  out  both  vagi  and  the  ganglion  stellatum.  Accordingly, 


334 


PHYSIOLOGY 


CHAP. 


it  cannot  depend  on  the  centrifugal  nerves  of  the  cardiac  plexus. 
After  dividing  the  splanchnic  nerve  the  depressor  effect  is  much 
less.  The  vascular  dilatation  must,  therefore,  take  place  largely 
in  the  vessels  controlled  by  this  nerve,  and  only  in  a  minor  degree 
in  other  vessels. 

These  results  were  confirmed  and  extended  by  various  observers 
on  the  cat,  horse,  dog,  and  pig.  In  poikilothermic  animals  no 
separate  depressor  nerves  could  be  discovered. 


FIG.  154. — Exposed  nerves  of  rabbit's  neck.  (Doyon  and  Morat.)  nv,  Vagus  nerve  ;  nd,  depressor 
nerve,  arising  above  in  two  brandies,  one  given  off  from  the  vagus  trunk,  the  other  from  the 
superior  laryngeal ;  nls,  superior  laryngeal  nerve  ;  nil,  inferior  or  recurrent  laryngeal  nerve  ; 
bes,  external  branch  of  spinal  nerve  ;  ni,  hypoglossal ;  gcs,  superior  cervical  ganglion  ;  sc,  cervi- 
cal sympathetic ;  gci,  inferior  cervical  ganglion  ;  etc,  carotid  artery ;  oas,  axillary  ganglion ; 
md,  digastric  muscle  ;  msi,  stylo-hyoid  muscle. 

Attempts  were  made  to  determine  the  exact  peripheral  distri- 
bution of  the  depressor  nerve.  Wooldridge  and  Kazem-Beck 
believed  that  its  fibres  entered  the  walls  of  the  ventricle ;  more 
recently  Koster  and  Tschermak  (1902)  discovered  that  its  nerve- 
endings  lay  in  the  wall  of  the  aorta. 

It  is  highly  probable  that  the  depressor  (which,  as  we  have 
said,  is  not  in  tonic  excitation)  is  only  excited  when  the  pressure 
in  the  aorta  becomes  excessive,  and  obstructs  the  systolic  evacua- 
tion of  the  heart.  The  vessels  then  dilate,  pressure  falls,  and  the 


ix  CAKDIAC  MUSCLE  AND  NEEVES  335 

resistance  which  the   heart  has  to  overcome   is   reduced.      The 
retarded  rhythm  tends  to  the  same  result. 

Some  interesting  experiments  of  Sewal  and  Steiner  illustrate 
this  theory.  On  ligaturing  the  two  carotids  they  observed  a  rise 
of  arterial  pressure,  which  was  obviously  nervous  in  origin,  since  it 
failed  when  the  vagi  had  previously  been  divided.  When,  on  the 
contrary,  the  depressors  alone  had  been  cut  before  ligaturing  the 
carotids,  a  much  greater  pressor  effect  was  obtained  than  with  the 
intact  depressors.  They  concluded  that  the  depressors  are  highly 
sensitive  to  any  increase  of  mechanical  resistance  presented  to  the 
functions  of  the  heart. 

In  studying  blood  pressure  during  asphyxia,  Konow  and 
Stenbeck  saw  that  it  was  far  more  irregular  when  the  depressors 
had  been  previously  divided  than  when  they  were  left  intact,  a 
proof  of  their  importance  in  the  regulation  of  the  circulation. 

Direct  proof  that  the  rise  in  aortic  pressure  stimulates  the 
depressors,  independent  of  cardiac  influence,  was  obtained  by 
Koster  and  Tscherniak  (1902).  They  showed  that  even  in  the 
isolated  heart  the  passive  distension  of  the  walls  of  the  aorta,  on 
filling  it  rapidly  with  artificial  fluid,  produced  stimulation  of  the 
depressors,  as  exhibited  in  a  negative  variation  (action  current)  of 
the  demarcation  current  led  off  from  two  points  of  the  nerve. 

Spallitta  and  Consiglio  endeavoured  to  ascertain  whether  the 
depressor  fibres  run  with  the  vagus  or  the  accessory.  After 
dividing  the  ramus  intern  us  of  the  accessory,  they  found  that 
excitation  of  the  depressors  produced  a  fall  of  blood  pressure,  but 
no  slowing  of  cardiac  rhythm.  The  depressors  accordingly  contain 
two  kinds  of  fibres :  one  set  cause  reflex  dilatation  of  the  vessels, 
and  belong  to  the  vagus  ;  the  other  reflexly  excites  the  inhibitory 
centre  of  cardiac  rhythm,  and  runs  in  the  accessory.  Mirto  and 
Pusateri  confirmed  these  results  by  histological  methods.  After 
intracranial  section  of  the  roots  of  the  accessory  nerve  they  found 
degenerated  fibres  in  the  depressor. 

The  afferent  fibres  from  the  heart  are  incapable  of  conveying 
clear  or  conscious  sensations.  This  was  shown  by  Harvey's 
experiments  on  the  exposed  heart  of  Viscount  Montgomery.  The 
indefinite  malaise  complained  of  in  the  cardiac  region  by  cardio- 
paths  (v.  Ziemssen)  may  result  from  compression  of  the  sensory 
nerves  beyond  the  heart.  Although  incapable  of  arousing 
conscious  sensations,  the  centripetal  cardiac  nerves  are  able 
reflexly  to  produce  more  or  less  diffuse  movements  of  the  skeletal 
muscles.  Budge,  Goltz,  Gurboki,  on  pinching  the  heart  in  rabbit 
and  frog,  obtained  these  reflex  movements,  which  failed  when 
the  vagi  had  been  divided. 

Even  such  afferent  fibres  of  the  vagus  as  do  not  belong  to  the 
heart  reflexly  modify  cardiac  rhythm.  If  the  central  end  of  one 
divided  vagus  is  stimulated  while  the  other  is  intact,  a  delayed 


336  PHYSIOLOGY  CHAP. 

rhythm  is  obtained,  which  does  not  appear  after  cutting  the  other 
vagus  (v.  Bezold,  Drechsfeld,  Aubert  and  Koever,  etc.).  The 
various  pulmonary  branches  of  the  vagus  were  stimulated,  accord- 
ing to  Hering,  by  insufflating  the  lungs  with  open  thorax, 
producing,  acceleration  of  cardiac  rhythm,  which  is  absent  with 
division  of  the  cervical  vagi.  The  acceleration  of  pulse  which 
Sommerbrodt  observed  in  man  after  screaming,  singing,  coughing, 
inhaling  of  compressed  air,  is  due  to  the  same  cause,  i.e.  to 
abnormal  rise  of  bronchial  pressure. 

Central  excitation  of  the  superior  laryngeal,  as  also  stimulation 
of  the  laryngeal  inucosa  above  the  vocal  cords,  produces  arrest  or 
slowing  of  the  heart-beat  with  intact  vagi  (Franc^ois-Franck). 
This  does  not  occur  with  centripetal  excitation  of  the  inferior 
laryngeal,  or  on  stimulation  of  the  laryngeal  mucosa  below  the 
vocal  cords. 

On  exciting  the,  abdominal  sympathetic  by  repeated  taps  of 
moderate  strength  on  the  belly  wall,  slight  inhibitory  phenomena 
are  readily  obtained  on  the  frog  (Goltz). 

The  sensory  branches  of  the  posterior  spinal  roots  have  a  double 
reflex  action  on  the  heart,  either  a  slowing  (Cl.  Bernard,  Frangois- 
Franck),  or  an  acceleration  of  rhythm  (Asp).  Central  excitation 
of  the  sciatic  plexus  by  mechanical  stimuli  provokes  inhibition,  by 
electrical  stimuli,  acceleration.  The  muscular  nerves  also  produce 
opposite  effects :  the  same  thing  produces  inhibition  with  a  strong 
stimulus,  acceleration  with  a  weaker  one.  When  chemically 
excited  (e.g.  by  inhalation  of  chloroform),  the  sensory  fibres  of  the 
trigeminus  readily  induce  slowing  and  even  arrest  of  the  heart,  and 
syncope,  which  has  a  great  practical  significance.  The  nerves  of 
the  special  senses  also  act  in  this  twofold  way  upon  the  heart. 

XII.  The  afferent  nerves  of  the  heart  affect  the  efferent 
through  centres  which  determine  the  reflex  effects. 

The  centre  of  the  diastolic  nerves  is  in  the  bulb  or  medulla 
oblongata  (E.  Weber,  Budge).  In  the  frog  it  extends  from  the 
optic  lobes  to  the  tip  of  the  calamus  scrip torius.  In  the  rabbit 
it  is  apparently  confined  to  the  bulb  (Frangois-Franck).  In  the 
cat  there  is  about  half-way  up  the  rhomboid  sinus,  a  point  at 
which  excitation  by  a  needle  produces  arrest  or  slowing  of  the 
heart  (Laborde). 

The  centre  for  the  systolic  nerves  has  up  to  the  present  not 
been  exactly  located.  The  whole  upper  section  of  the  cervical 
cord  reacts  by  acceleration  of  cardiac  rhythm^ 

Although  the  paths  are  not  yet  exactly  determined,  it  must 
be  remembered  that  the  cardiac  centres  are  in  connection  with 
the  cortical  and  subcortical  centres  of  the  brain.  The  influence 
of  psychical  states  upon  the  heart  is  undeniable ;  some  people 
even  have  the  faculty  of  voluntarily  influencing  their  heart-beats. 

It   is   probable    that    under   normal   conditions    the   cardiac 


ix  CAEDIAC  MUSCLE  AND  NERVES  337 

centres  are  in  continuous  slight  excitation,  on  which  depends  the 
tone  of  the  vagi,  exhibited  in  the  acceleration  of*  the  beats,  on 
simple  division  of  that  nerve,  or  administration  of  atropin.  This 
effect  does  not  appear  when  section  of  the  vagus  is  preceded  by 
division  of  the  cervical  cord  (Bernstein).  Acceleration  is  also 
obtained  after  dividing  the  splanchnic  nerve  (Asp),  due  not 
to  the  lowering  oT  blood  pressure,  which  usually  produces  the 
opposite  effect,  but  to  the  depression  of  vagal  tonus.  In  the 
newborn,  tonicity  seems  to  be  wanting  in  the  vagus  till  after  the 
second  week,  since  in  kittens  neither  section  of  the  vagus  nor 
exhibition  of  atropine  causes  acceleration  of  pulse  (Soltmann). 

It  is  possible  that  the  systolic  nerves  and  centres  also  have 
normally  a  certain  tonicity,  although  subordinate  to  the  diastolic 
nerves.  After  extirpation  of  the  lower  cervical  and  stellate 
ganglia  on  both  sides,  there  is,  when  the  vagi  are  divided,  a 
marked  acceleration  of  rhythm  (Tschirjew,  Strieker,  and  Wagner). 
With  intact  vagi,  a  permanent  slowing  of  beat  can  be  obtained 
on  dividing  the  accelerators  (Timofeew). 

The  tone  of  the  cardiac  centres  and  nerves  may  be  automatic  or 
reflex,  or  as  is  most  probable,  automatic  and  reflex  in  character.  It 
is  known  that  the  frequency  of  cardiac  rhythm  normally  stands 
in  inverse  ratio  to  the  height  of  the  average  arterial  blood  pressure, 
i.e.  that  rise  of  blood  pressure  produces  lowering  of  pulse  frequency 
and  vice  versa.  After  section  of  the  vagi  this  ratio  is  no  longer 
so  distinct  and  constant,  showing  that  the  blood-pressure  regulates 
the  tone  of  the  cardiac  nerve  centres,  those  of  the  vagus  in 
particular,  directly  or  reflexly. 

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A.  J.  CARLSON  and  W.  J.  MEEK.     On  the  Mechanism  of  the  Embryonic  Heart 

Rhythm  in  Limulus.     Amer.  Journ.  of  Physiol.,  1908,  xxi.  1. 
W.    H.    HOWELL  and   W.    W.  DUKE.     The  Effect  of  Vagus   Inhibition   on   the 

Output  of  Potassium   from   the   Heart.      Amer.    Journ.    of  Physiol.,    1908, 

xxi.  51. 


340  PHYSIOLOGY  CHAP,  ix 

W.  J.  MEEK.     The  Relative  Resistance  of  the  Heart  Ganglia,  the  Intrinsic  Nerve 

Plexus,  and   the  Heart  Muscle  to  the  Action  of  Drugs.     Amer.  Journ.    of 

Physiol.,  1908,  xxi.  230. 
W.   H.    SCHULTZ.     Studies   in  Heart   Muscle.     The   Refractory   Period   and   th/ 

Period  of  Varying  Irritability.     Amer.  Journ.  of  Physiol.,  1908,  xxii.  133. 
A.    J.    CARLSON.     Comparative    Physiology  of  the    Invertebrate  Heart.     Part  X. 

Amer.  Journ.  of  Physiol.,  1908,  xxii.  353. 
H.    J.    B.    FRY.      The   Influence  of    the   Visceral  Nerves    upon  the    Heart   in 

Cephalopods.     Journ.  of  Physiol.,  1909-10,  xxxix.  184. 
J.  ERI.ANGER.     Can  Functional  Union  be  re-established  between  the  Mammalian 

Auricles  and  Ventricles  after   Destruction  of  a   Segment  of  the   Auriculo- 

Ventricular  Bundle?     Amer.  Journ.  of  Physiol.,  1909,  xxiv.  375. 


CHAPTEE  X 

PHYSIOLOGY  OF  VASCULAK  MUSCLE  AND  NERVES 

SUMMARY. — 1.  Discovery  of  vasomotor  nerves.  2.  Vascular  tone  and  its 
rhythmic  and  a-rhythmical  variations,  as  depending  essentially  upon  the  automatic 
and  reflex  excitability  of  the  smooth  muscle  cells.  3.  Theory  of  vaso-constrictor 
nerves.  4.  Theory  of  vaso-dilator  nerves.  5.  Vascular  reflexes.  6.  Bulbar  vaso- 
constrictor centre.  7.  Spinal  and  cerebral  centres  for  vaso-constrictor  nerves. 
8.  Centres  for  vaso-dilator  nerves.  Bibliography. 

THE  preceding  chapter  on  the  physiology  of  cardiac  muscle  and 
the  cardiac  nerves  will  facilitate  our  investigation  of  the  physiology 
of  the  muscle  cells  and  nerves  with  which  the  walls  of  the  blood- 
vessels are  provided.  As  we  shall  see,  there  is  an  exact  analogy 
between  the  physiological  phenomena  in  both  cases. 

I.  After  Haller,  Spallanzani,  Magendie,  and  Poiseuille  had 
demonstrated  the  possibility  of  the  circulation  of  the  blood,  in 
virtue  simply  of  the  heart's  activity  as  a  force-pump,  and  the 
physical  elasticity  of  the  blood-vessels,  the  older  theories  as  to  the 
importance  to  the  circulation  of  the  muscle  cells  and  vascular 
nerve  fibre  were  disregarded  and  almost  forgotten.  At  the 
commencement  of  the  last  century,  however,  certain  normal  and 
pathological  phenomena,  which  directly  contradicted  the  purely 
mechanical  theory,  again  attracted  the  attention  of  physicians 
and  physiologists.  Among  these  are :  abnormal  conditions  of 
temperature  and  nutrition  in  paralysed  limbs,  circulatory  changes 
(blushes  and  pallor)  due  to  emotional  states  or  to  neuralgia, 
hyperaemia,  and  congestion  at  the  seat  of  inflammation,  pneumonia 
after  section  of  the  vagi,  panophthalmia  on  dividing  the  trigeminal, 
failure  of  erection  o/  penis,  when  the  spinal  nerves  have  been 
divided,  and  so  on. 

The  precursors  of  the  physiology  of  the  active  movements  of 
the  vessels  included  E.  H.  Weber  (1831),  Henle  (1840),  Stilling 
(1840),  Valentin  and  Schiff  (1844),  who  adumbrated  not  a  few  of 
the  facts  and  theories  which  subsequently  received  experimental 
confirmation. 

In  1851  Claude  Bernard  discovered  and  described  the 
phenomena  that  occur  in  the  vessels  of  the  rabbit's  ear,  on 

341 


342  PHYSIOLOGY  CHAP. 

division  of  the  cervical  sympathetic,  after  which  the  notion  of 
vascular  nerves  became  familiar.  Cl.  Bernard  was  more  struck 
by  the  marked  rise  of  temperature  in  all  parts  supplied  by  the 
sympathetic  than  by  the  dilatation  of  the  vessels,  so  much  so 
that  in  1852  he  gave  an  erroneous  interpretation  of  the  same, 
declaring  the  sympathetic  to  be  a  thermal  nerve.  Shortly  after- 
wards, however,  Brown  -  Se'quard  completed  the  discovery  by 
describing  the  converse  phenomena  that  occur  in  the  vessels  of 
the  ear,  when  the  peripheral  end  of  the  divided  nerve  is  excited 
by  an  electrical  stimulus.  This  he  rightly  interpreted  as  meaning 
that  the  primary  effects  were  dilatation  and  constriction  of  the 
vessels,  the  secondary  effects,  the  warming  or  cooling  of  the  parts 
supplied ;  and  he  gave  the  name  of  vaso-constrictors  to  the  rami 
auriculares  of  the  cervical  sympathetic  system.  A.  Waller  almost 
simultaneously  confirmed  these  same  facts  and  their  significance, 
without  knowing  of  Brown-Sequard's  publication. 

In  1854,  M.  Schiff,  observing  the  vessels  of  the  rabbit's  ear  by 
transmitted  light,  described  an  irregular  succession  of  contractions 
and  dilatations,  which  are  much  slower  than  the  rhythm  of  the 
heart,  and  quite  independent  of  it.  Owing  to  these  undulations, 
the  flow  of  blood  through  the  ear  alternately  diminishes  and 
increases  (ischaemia  and  hyperaemia),  with  a  consequent  fall  and 
rise  of  its  temperature,  blood  pressure,  and  volume. 

In  1856  he  showed  indirectly  that  besides  the  vaso-constrictors, 
vaso-dilators  are  also  present  in  the  cervical  sympathetic,  so  that 
the  rhythm,  which  he  detected  in  the  vessels  of  the  ear,  must  be 
regarded  as  the  result  of  the  alternate  functional  predominance 
of  one  or  other  kind  of  vasomotor  nerve.  He  found  when  the 
animal  was  artificially  warmed  some  days  after  dividing  the 
cervical  sympathetic,  or  was  forced  to  take  violent  movements,  or 
infected  with  a  septic  or  toxic  fever,  that  the  vessels  of  the  ear 
on  the  normal  side  showed  much  greater  vascular  dilatation, 
hyperaemia  and  heating  than  those  on  the  operated  side,  a  fact 
which  led  Schiff  to  the  conclusion  that  the  former  were  under 
the  control  of  dilator  nerves,  which  in  the  second  case  had  been 
divided. 

SchifFs  view  was  brilliantly  confirmed  in  1858  by  Claude 
Bernard,  who  discovered  the  effect  produced  in  the  vessels  of  the 
submaxillary  gland  of  the  dog,  by  electrical  stimulation  of  that 
branch  of  the  facial  nerve  which  traverses  the  tympanic  cavity, 
joins  the  lingual  branch  of  the  trigeminal,  and  then  under  the 
name  of  chorda  tympani  passes  partly  into  the  tongue,  partly  to 
the  submaxillary  and  sublingual  glands.  That  the  chorda 
tympani  contains  vaso-dilator  fibres  is  shown  by  the  fact  that  its 
stimulation  produces  marked  hyperaemia  of  all  the  vessels  of  the 
submaxillary  gland,  associated  with  such  marked  acceleration  of 
the  blood-stream  that  the  flow  through  the  glands  has  scarcely 


x  VASCULAR  MUSCLE  AND  NERVES  343 

time  to  acquire  the  characteristics  of  venous  blood,  while  the 
pulse  wave  of  the  arteries  passes  beyond  the  capillaries,  and 
reaches  the  small  veins  (Fig.  155). 

There  are,  accordingly,  constrictor  and  dilator  nerves  to  the 
blood-vessels :  the  former  correspond  to  the  systolic,  the  latter  to 
the  diastolic,  nerves  of  the  heart.  Vascular  rhythm  and  tonicity 
are  analogous  to  cardiac  rhythm  and  tonicity.  Just  as  the 
innervation  of  the  heart  regulates  the  circulation  as  a  whole,  so 
the  innervation  of  the  vessels  regulates  the  circulation  in  the 
several  vascular  regions.  The  same  questions  as  were  examined 


FIG.  155.— Operative  procedure  for  exposing  submaxillary  gland,  duct,  nerves  and  vessels. 
(Cl.  Bernard.)  Gsm,  Submaxillary  gland  ;  D?c,  Wharton'.s  duct,  into  which  a  glass  cannula  is 
inserted  to  draw  off  the  saliva  secreted  by  the  gland ;  Db,  Bertholin's  duct  to  sublingual ; 
Nl,  lingual  nerve  ;  Ct,  chorda  tympani,  running  to  gland  along  with  excretory  duct ;  C,  carotid 
accompanied  by  small  nerve  branches  of  sympathetic  ss  ;  Vje,  external  .jugular  vein  ;  V, 
efferent  vein  from  gland  ;  Ni,  hypoglossal  nerve  ;  Md,  anterior  half  of  digastric  muscle,  lifted 
by  hook  ;  Mmj,  mylo-hyoid  muscle,  cut  so  as  to  expose  the  lingual  nerve,  and  excretory  ducts 
beneath  it ;  Mn,  maseter  muscles. 

and  discussed  in  studying  the  active  movements  of  the  heart 
crop  up  in  the  study  of  the  active  movements  of  the  vessels. 
We  must  therefore  consider  separately  the  rhythm  and  the  tone 
of  the  vessels,  the  vaso-constrictors,  and  the  vaso-dilators,  in  the 
better-known  vascular  regions. 

II.  The  slow  rhythm  of  dilatation  and  constriction,  as  first 
described  by  Schiff  for  the  vessels  of  the  rabbit's  ear,  is  no  isolated 
phenomenon.  It  was  observed  by  Wharton  Jones  in  the  vessels  ot 
the  bat's  wing,  by  Saviotti  on  the  frog's  peritoneal  arteries,  by 
Riegel  in  the  small  mesenteric  arteries  and  web  of  the  same 
animal.  In  this  category  must  also  be  included  the  long  irregular 
waves  "of  the  third  order,"  which  are  independent  of  cardiac  rhythm 
and  respiratory  movements,  and  were  first  noted  in  blood-pressure 


344 


PHYSIOLOGY 


CHAP. 


curves  by  Traube  and  Hering.  Lastly  (1875),  Mosso  found  with 
his  plethysmograph  (Fig.  156)  that  the  volume  of  the  human  fore- 
arm exhibits  the  same  long  and  irregular  oscillations,  which  can 
only  be  interpreted  as  the  effects  of  a  peculiar  rhythm  of  alternate 
contractions  and  dilatations  of  the  vessels  of  the  limb.  Von  Basch 

n 


FIG.  156.— Mosso's  plethysmograph,  for  recording  slow  variations  in  volume  of  vessels  of  fore- 
arm (diagram).  A,  B,  glass  cylinder  to  receive  the  forearm,  closed  by  rubber  band ;  this 
rests  on  the  board  E,  which  is  suspended  from  the  ceiling  by  a  wire  ;  C,  opening  closed  with  a 
cork,  through  which  the  cylinder  can  be  filled  with  lukewarm  water ;  D,  opening  through 
which  a  thermometer  is  passed,  showing  temperature  of  water  ;  F,  G,  tube  through  which  the 
cylinder  containing  the  forearm  communicates  with  the  small  cylinder  M,  which  floats  above 
the  level  of  the  fluid  ft,  b,  contained  in  large  vessel  P ;  N,  lead  weight  carrying  the  pen  to  write 
on  moving  cylinder  of  kymograph,  which  counterpoises  M,  with  which  it  is  connected  by  two 
silk  threads  passing  over  the  double  pulley  L ;  H,  J,  burette  that  can  be  raised  or  lowered  in 
adding  or  changing  the  water  in  the  float.  The  instrument  works  as  follows  :  when  the  vessels 
of  the  forearm  contract,  an  amount  of  water  corresponding  with  the  diminution  in  volume  is 
aspirated  from  the  float  M  to  the  cylinder  A,  B  ;  this  raises  the  float  and  depresses  the  counter- 
poise N,  which  records  the  diminution  of  volume  on  the  revolving  cylinder.  When,  on  the  con- 
trary, the  vessels  of  the  forearm  dilate,  a  quantity  of  water  in  the  cylinder  A,  13  is  driven  out 
into  M,  so  that  it  sinks,  and  N  is  raised,  recording  the  increase  of  volume.  To  avoid  positive 
or  negative  pressure  above  the  forearm  immersed  in  the  cylinder  A,  B,  care  must  be  taken 
that  its  upper  level  is  at  the  same  level  a,  b  as  the  water  contained  in  the  receiver  P  where  M 
is  floating. 

(1876)  confirmed  Mosso's  facts  with  a  weighing  plethysmograph, 
which  gives  more  relative  values  than  Mosso's  apparatus.  From 
all  these  observations  it  appears  probable  that  the  autochthonous 
rhythm  of  the  vessels  is  common  to  many  other  vascular  tracts 
that  have  not  yet  been  fully  examined  (Figs.  157  and  158). 

It  must  not,  however,  be  assumed  that  rhythmical  activity  is 
continuous  and  constant  in  all  vascular  regions :  in  most  cases, 
indeed,  the  microscopic  study  of  transparent  vascular  tracts  shows 


VASCULAR  MUSCLE  AND  NERVES 


345 


B     C 


no  alteration  in  the  diameters  of  the  vessels,  which  may  remain 
for  a  considerable  time  in  the  state  intermediate  between  excessive 
dilatation  and  excessive  constriction,  which  is  commonly  known  as 
tonus  or  tonic  contraction  of  the  vessels. 

Vascular  rhythm,  being  much  slower  and  less  regular,  does  not 
correspond  with  the  functional  rhythm  of  the  heart,  i.e.  with  the 
alternation  of  cardiac  systole  and  diastole.  On  the  other  hand,  it 
does  correspond,  and  is  in  strict  analogy,  with  the  tonic  rhythm 
discovered  by  Fano  in  the  walls  of  the  tortoise  auricle,  and  results 
from  the  alternate  contraction  and  expansion  of  the  sarcoplasm  of 
the  smooth  spindle-shaped  muscle  cells  of  the  tunica  media, 
particularly  in  the  small  arteries. 

The  tone  and  rhythmical  activity  of  the  Veins  is  obscure,  and 
has  been  little  studied;  their 
muscular  cells  are  few  in  number, 
and  vary  considerably  in  differ- 
ent regions  and  tissues.  The 
veins  of  the  bones  and  brain 
have  no  contractile  elements ; 
the  veins  of  the  portal  system 
are  highly  muscular  It  is  only 
at  the  extreme  ends  of  the  venae 
cavae  and  pulmonary  veins, 
where  they  open  into  the  aur- 
icles, that,  in  addition  to  a 
perhaps  slowly  varying  tonus, 
we  find  any  rapid  and  fairly 
regular  rhythmicalactivity,such 
as  gives  rise  to  the  systolic  and 
diastolic  rhythm  of  the  heart. 

The  autochthonous  activity  of  the  vessels,  whether  tonic  or 
rhythmic,  resembles  that  of  the  heart,  in  being  automatic,  i.e. 
independent  of  external  stimuli  acting  on  the  muscle  cells. 
This  conclusion  is  reached,  not  merely  by  analogy,  which  in  this 
instance  is  of  great  value,  but  also  by  direct  observation,  from 
which  every  unbiased  observer  must  perceive  that  the  oscillations 
of  tone  in  the  vessels  of  the  rabbit's  ear  are  independent  of 
changes  in  external  conditions.  It  is  uncertain  whether  the 
tonic  and  rhythmic  activity  of  the  vessels  is,  like  that  of  the 
heart,  an  inherent  property  of  the  muscle  cells,  as  claimed  by 
the  myogenists,  or  whether  it  is  brought  about  by  the  peripheral 
ganglia  and  nerve  fibres  which  are  particularly  abundant  in  the 
walls  of  the  arteries,  where  they  form  a  delicate  plexus  round 
the  smooth  muscle  cells.  Experience  shows  that  the  neuro- 
paralytic  hyperaemia  and  rise  of  temperature  consequent  on  the 
division  of  all  the  nerves  of  the  limb  does  not  persist,  but  dis- 
appears gradually,  so  that  after  some  days  the  paralysed  limb  is 


FK;.  157.— Tracings  obtained  with  plethysmograph 
of  Fig.  1.06.  (MOSSO.)  The  revolving  drum  is 
moved  on  a  short  distance  at  each  minute,  so 
that  the  writing  point  traces  a  horizontal  line. 
The  variations  in  volume  that  occur  during  the 
minute  in  which  the  drum  is  stationary  are 
indicated  by  vertical  lines,  which  show  the 
extent  of  the  oscillations  in  volume  during  that 
period.  In  this  case  each  cm.  in  height  from 
the  ordinate  corresponds  to  2  c.c.  of  blood.  At 
P,  P  the  subject  replied  to  questions  put  by 
the  experimenter.  At  A  he  raised  his  left  hand 
to  rub  his  nose,  at  B  to  rub  his  ear.  At  C  he 
heard  the  sound  of  an  electric  bell. 


346 


PHYSIOLOGY 


CHAP. 


more  ischaemic  and  cooler  than  the  healthy  limb  on  the  opposite 
side  (Goltz  and  others).  This  means  that  the  muscle  cells,  or 
peripheral  ganglionic  elements,  may,  independent  of  the  nerve 
centres,  acquire  a  degree  of  tonic  contraction  in  excess  of  the 
normal.  On  the  other  hand  we  know  that  even  excised  organs, 
e.g.  the  dog's  kidney,  artificially  circulated,  exhibit  with  the 


FIG.  loS. — Plethysmogram  of  forearm,  obtained  by  connecting  the  cylinder,  A,  B,  of  plethysmo- 
graph  with  a  Marey's  writing  tambour.  (Mosso.)  -  The  rotating  drum  moves  at  uniform  speed. 
The  experiment  was  performed  in  an  iron  room,  where  the  air  could  be  compressed  to  various 
measurable  pressures.  Each  tracing,  in  addition  to  the  plethysmograms  of  the  pulse,  shows 
the  slow  oscillations  in  volume  of  the  forearm  which  depend  on  the  oscillations  of  vascular 
tone.  1,  Tracing  made  before  compression  of  air;  2,  at  KX)  mm.  Hg  compression;  3,  at 
100  mm.  Hg  ;  4,  at  80  mm.  Hg  ;  5,  at  50  mm.  Hg  ;  6,  at  ordinary  barometric  pressure  ;  7,  two 
minutes  alter  return  to  ordinary  barometric  pressure  ;  8,  a  quarter  of  an  hour  later. 

plethysniographic  method  constant  irregular  oscillations  of 
volume,  which  obviously  depend  on  oscillations  of  tone  in  the 
renal  vessels  (Mosso,  1874). 

A  similar  effect  was  noted  by  Bernstein  in  the  amputated 
paw  of  the  dog.  So,  too,  the  work  of  Bayliss  (1901),  on  the 
reaction  of  certain  blood-vessels  to  changes  of  blood  pressure, 
shows  that  the  vascular  muscles  are  capable  of  altering  their 
tone  independent  of  the  nervous  system.  Bayliss  found  on 
recording  the  changes  in  volume  of  the  hind  limb  of  an  animal, 


x  VASCULAK  MUSCLE  AND  NERVES  347 

completely  separated  from  the  central  nervous  system  by  the 
plethysmograph,  that  artificial  depression  of  blood  pressure- 
caused  by  compression  of  the  abdominal  aorta,  or  by  stimulating 
the  peripheral  trunk  of  the  vagus,  or  depressor  nerve — produced 
an  initial  shrinkage  of  volume.  Even  during  the  fall  of  blood 
pressure,  however,  there  was  a  gradual  return  to  the  earlier 
volume,  while  after  normal  pressure  was  restored  there  was  a 
marked  increase  in  volume,  a  proof  that  the  vessels  reacted  to 
the  fall  of  blood  pressure  by  a  definite  dilatation.  Artificial 
rise  of  blood  pressure  (e.g.  from  stimulation  of  the  splanchnic) 
produced  constriction  of  the  vessels  of  the  limb. 

The  muscular  coat  of  the  vessels  (like  the  muscular  wall  of 
the  heart)  is  automatically  active  both  in  constriction  and  in 
dilatation — the  former  caused  by  the  shortening,  the  latter  by 
the  lengthening  or  expansion  of  the  sarcoplasm  of  the  spindle- 
shaped  muscle  cells.  This  hypothesis,  which  found  little  favour 
when  we  propounded  it  in  1871-73,  as  the  logical  deduction 
from  Weber's  theory  of  muscular  elasticity,  is  now,  on  the 
strength  of  recent  work  on  the  automatic  rhythmicity  of  the 
cardiac  muscle  cells  (that  of  Gaskell  and  Engelmann  in  particular), 
not  only  unopposed,  but  even  included,  in  many  modern  text- 
books. "  We  have  repeatedly  insisted  "  (says  Foster  l)  "  that  the 
relaxation  of  a  muscular  fibre  is  as  much  a  complex  vital 
process,  is  as  truly  the  result  of  the  metabolism  of  the  muscular 
substance,  as  the  contraction  itself ;  and  there  is  a  priori  no  reason 
why  a  nervous  impulse  should  not  govern  the  former  as  it  does 
the  latter." 

Vascular  tonicity  and  its  slow  rhythmical  oscillations  (Fig. 
158)  are  probably  inherent  properties  of  the  smooth  muscle 
cells  and  the  vascular  nerves  that  direct  and  regulate  them, 
since  they  exert  a  double  and  opposite  influence,  katabolic  and 
anabolic,  upon  the  metabolism  of  muscle.  The  vaso-constrictors 
function  by  promoting  the  dissimilatory  processes;  the  vaso- 
dilators, on  the  contrary,  by  favouring  the  assimilatory  processes 
of  cellular  sarcoplasm.  The  first  are  therefore  katabolic,  the 
second  anabolic  nerves  to  the  vessels.  The  active  movements  of 
the  vessels  are  thus  regulated  by  mechanisms  perfectly  analogous 
to  those  which  govern  the  active  movements  of  the  heart. 

III.  It  is  known,  on  the  strength  of  numerous  experiments, 
that  every  vascular  region  is  supplied  with  vaso-constrictor  nerves. 
This  is  plain  on  recapitulating  the  most  important  heads  of  the 
copious  literature  of  the  subject. 

The  great  splanchnic  nerve  contains  numerous  constrictor 
fibres  which  supply  the  most  extended  area,  since  it  controls  the 
blood-vessels  of  the  greater  portion  of  the  abdominal  viscera. 
Ludwig  and  Cyon  (1866),  v.  Bezold  and  Bever  (1867),  found 

1  Text-Book  of  Physiology,  Part  I.  p.  313,  5th  ed.,  1888. 


348  PHYSIOLOGY  CHAP. 

that  division  of  this  nerve  produced  a  marked  fall  of  lateral 
pressure  in  the  aorta,  while  stimulation  of  the  peripheral  end 
of  the  divided  nerve  raised  the  pressure  above  that  which 
obtained  before  section.  On  investigating  the  state  of  the 
visceral  vessels  after  section,  marked  congestion  was  observed 
in  the  venous  portal  system,  with  distinct  hyperaemia  of  the 
small  vessels  of  the  mesentery,  intestinal  canal,  and  renal 
parenchyma.  These  effects  are  more  pronounced  in  the  rabbit 
than  in  the  dog  (Asp),  apparently  because  in  herbivores  the 
gastric  canal  is  much  longer  than  in  carnivores. 

The  constrictor  fibres  of  the  splanchnic  run  to  the  coeliac 
plexus,  and  thence  to  the  stomach,  intestines,  and  kidneys. 
Excitation  of  the  splanchnic  on  one  side  only  causes  the  vessels 
of  both  kidneys  to  contract  (Cohnheim  and  Boy). 

The  constrictor  fibres  of  the  hepatic  vessels  also  emerge  from 
the  splanchnic,  and  pass  to  the  coeliac  plexus,  and  thence  to  the 
liver,  along  the  bile-duct  and  hepatic  artery  (Vulpian).  The 
vaso-constrictors  of  the  spleen  come  from  the  left  splanchnic, 
and  perhaps  also  from  the  right  (Roy). 

It  is  known  from  other  observations  that  the  great  splanchnic 
does  not  contain  all  the  vaso-constrictor  fibres  of  the  abdominal 
viscera.  The  lesser  splanchnic  has  fibres  of  the  same  character 
(Asp),  and  the  abdominal  branches  of  the  vagus  also  appear  to 
contain  vaso-constrictors  for  the  spleen  (Oehl). 

Next  to  the  great  splanchnic,  the  vaso-constrictor  nerve 
which  supplies  the  most  extended  tract  is  certainly  the  cervical 
sympathetic,  which  not  only  regulates  tonicity  in  the  vessels  of 
the  ear,  as  discovered  by  Claude  Bernard,  but  also  exerts  its 
constrictor  function  on  all  other  external  and  internal  vessels  of 
the  head,  as  appears  from  the  investigations  of  several  observers. 

It  was  plain  from  the  work  of  Budge  and  Waller  (1853)  that 
the  constrictor  fibres  of  the  cervical  sympathetic  did  not  arise  in 
the  ganglia  situated  along  its  course,  but  in  the  anterior  roots  of 
the  spinal  nerves,  whence  they  emerged  by  the  raini  communi- 
cantes.  The  constrictor  fibres  run  principally  with  the  vessels 
round  which  they  form  a  plexus ;  but  they  are  partly  associated 
with  the  cerebral  nerves,  leaving  them  again  later,  to  join  the 
vessels.  Thus  the  hypoglossal  and  lingual  branches  of  the 
trigeminal  contain  vaso-constrictor  fibres  for  the  tongue  (Vulpian). 
The  facial  nerve,  again,  contains  many  fibres  of  the  same  kind,  so 
that  division  of  this  nerve  is  followed  by  a  rise  of  temperature  in 
the  whole  face  (CL  Bernard).  These  vaso-constrictor  fibres  do 
not  originate  in  the  centres  of  the  cerebral  nerves,  seeing  that 
destruction  of  these  centres  produces  no  sign  of  vascular  paralysis. 
They  probably  emerge  from  the  sympathetic. 

It  is,  however,  possible  that  besides  the  constrictor  fibres  from 
the  sympathetic,  the  vessels  of  the  head  are  affected  by  other 


x  VASCULAK  MUSCLE  AND  NERVES  349 

constrictor  fibres,  the  origin  of  which  is  not  yet  determined. 
Thus,  e.g.,  the  vessels  of  the  ear  also  receive  constrictors  from  the 
second  and  third  nerves  of  the  cervical  plexus  (Schiff,  Loven,  etc.). 

The  vaso-constrictors  of  the  limbs  run  principally  to  the 
cutaneous  vessels,  the  vessels  of  the  muscles  being  less  well 
supplied  with  motor  nerves  (Sadler,  Hafiz,  Grtitzner  and  Heiden- 
hain,  and  others). 

The  vaso-constrictors  of  the  fore-limbs  originate  in  the  anterior 
roots  of  the  median  tract  of  the  thoracic  cord  (third  to  seventh 
nerves),  join  the  sympathetic,  and  unite  at  the  first  thoracic 
ganglion  with  the  ramifications  of  the  brachial  plexus.  The 
cervical  roots  which  contribute  to  the  formation  of  this  plexus 
contain  no  vaso-cons  trie  tor  fibres  (01.  Bernard,  Cyon,  etc.).  Some 
of  these  fibres  accompany  the  vessels  of  the  limb  directly,  without 
joining  the  branches  of  the  brachial  plexus  (Vulpian). 

The  vaso-constrictors  of  the  lower  limbs  have  been  more 
studied.  They  emerge,  not  from  the  roots  of  the  lower  segment  of 
the  cord,  but  from  the  thoracic  tract  and  upper  segment  of  the 
lumbar  cord,  particularly  from  the  eleventh,  twelfth,  and  thirteenth 
dorsal,  and  the  first  and  second  lumbar  nerves  (Bayliss  and 
Bradford).  They  pass  by  the  rami  communicant es  to  the  thoracic 
and  abdominal  sympathetic,  then,  for  the  most  part,  joining  the 
great  nerve  trunks  to  the  limbs,  the  sciatic  especially ;  while  a  few 
only  accompany  the  vessels  of  the  limbs  direct  from  the  abdominal 
ganglia. 

It  is  clear  from  the  consensus  of  observations  on  the  vaso- 
constrictors in  different  regions  that  they  originate  principally  in 
the  anterior  roots  of  the  dorsal  tract  of  the  cord,  pass  by  way  of 
the  rami  communicantes  to  the  ganglion  sympathetic  system,  and 
thence  run  directly  or  indirectly  to  the  vessels,  where  they  form  a 
fine  plexus  round  the  muscular  tunica  media.  Their  excitability 
is  less,  and  their  latent  period  longer  than  that  of  the  motor  nerves 
to  the  skeletal  muscles,  and  they  are  constantly  in  a  certain  state 
of  activity,  on  which  the  tone  of  the  vessels  depends.  Section  of 
these  nerves  accordingly  produces  vascular  atony  and  subsequent 
hyperaemia,  while  excitation  of  the  peripheral  cord  produces 
constriction  or  vascular  hypertonia  and  subsequent  ischaemia. 

What  modifications  in  local  blood  pressure  and  velocity  of 
circulation  are  produced  by  such  hyperaemia  or  ischaemia  ?  Little 
was  known  definitely  before  Dastre  and  Morat  published  their 
observations  on  the  horse.  They  employed  two  sphygmoscopes, 
one  applied  to  the  facial  artery,  the  other  to  the  facial  vein  of  the 
animal.  They  found  that  Hgation  or  section  of  the  cervical 
sympathetic  caused  a  fall  of  blood  pressure  in  the  artery,  and  a 
rise  in  the  vein  (local  circulatory  delay).  Stimulation  of  the  nerve, 
on  the  contrary,  produced  rise  of  arterial  and  fall  of  venous 
pressure  (local  acceleration  of  circulation),  folio  wed  by  the  contrary 


350  PHYSIOLOGY 


CHAP. 


phenomenon,  viz.  fall  of  arterial  and  rise  of  venous  pressure, 
greater  than  that  which  occurs  on  simple  division  of  the  nerve 
(local  circulatory  delay)  in  consequence  of  fatigue  (Fig.  159). 

The  fact  of  vascular  ultra-dilatation  is  very  interesting,  as  it 
implies  that  strong  and  persistent  excitation  of  the  nerve  exhausts 
the  peripheral  ganglia,  and  thus  depresses  the  tone  which  these 
maintain  in  the  vessels  even  after  the  nerve  has  been  divided. 

IV.  Since  1874,  the  theory  of  vaso-  dilator  nerves  has  been 
much  developed.  Next  to  Bernard's  discovery  of  the  vaso- 
dilator fibres  contained  in  the  chorda  tynipani  (referred  to 
above),  the  discovery  of  the  nervi  erigentes  of  the  penis  by 
Eckhardt  (1863)  demands  special  mention.  These  nerves  are 


FIG.  159. — Effect  on  arterial  and  venous  pressure  in  facial  vessels  of  electrically  exciting  the 
peripheral  trunk  of  horse's  cervical  sympathetic.  (Dastre  and  Morat.)  Af,  tracing  of  blood 
pressure  in  peripheral  trunk  of  facial  artery  ;  Vft  of  facial  vein.  The  excitation  took  place  at 
the  part  between  the  two  vertical  lines,  marked  on  abscissa  by  an  electric  signal  separate  from 
that  which  shows  the  time  in  seconds.  The  tracings  show  tnat  stimulation  of  the  sympathetic 
is  followed  by  a  rise  of  arterial  and  fall  of  venous  pressure  (preceded  by  temporary  rise  due 
to  increased  outflow),  which  is  succeeded  by  the  opposite  effect,  i.e.  fall  of  arterial,  and  rise 
of  venous  pressure,  due  to  extra-dilatation  of  vessels. 

branches  from  the  sacral  plexus,  which,  when  peripherally  stimu- 
lated, cause  erectile  swelling  of  the  corpora  cavernosa,  due  not 
to  obstruction  of  the  venous  outflow,  but  to  increased  arterial 
influx,  owing  to  active  dilatation  of  the  helicine  arteries.  These 
two  discoveries,  however,  remained  isolated  for  more  than  a  decade, 
and  Goltz  (1874)  was  the  first  to  suggest  that  the  dilators,  like 
the  constrictors,  were  distributed  to  every  vascular  region,  the 
difficulty  of  experimental  proof  arising  from  the  fact  that  they 
nearly  always  run  jointly  with  the  constrictor  fibres,  which  by 
their  prevailing  influence  on  the  tone  of  the  vessels  mask  the 
antagonistic  action  of  the  dilators. 

For  this  reason  it  cannot  be  decided  'whether  the  dilator  nerves 
are,  like  the  constrictors,  in  tonic  activity ;  section  of  the  chorda 
tynipani  or  nervi  erigentes  produced  no  perceptible  constriction  of 
the  vessels  to  which  they  are  distributed. 


x  VASCULAR  MUSCLE  AND  NERVES  351 

There  has  been  much  discussion  as  to  whether  the  sciatic  trunk 
contains  vaso- dilator  fibres.  Goltz  and  others  noted,  as  the 
primary  effect  of  dividing  the  nerve,  the  atonic  dilatation  of  the 
vessels  in  the  limb,  exhibited  principally  in  the  increased 
temperature  of  the  paw  ;  while  the  primary  effect  of  peripheral 
stimulation  is  vascular  constriction,  shown  chiefly  in  the  cooling  of 
the  same — as  also  by  increased  blood  pressure  in  the  small  arteries 
of  large  animals  (Fig.  160).  Shortly  after  the  section  of  the 
sciatic,  however,  the  paralysed  limb  cools  off  gradually,  till  at  the 
end  of  a  few  days  it  is  colder  than  the  healthy  leg,  probably  because 
the  peripheral  ganglia  are  capable,  even  when  separated  from  the 
spinal  centres,  of  recovering  their  vascular  tone  until  it  exceeds 
the  normal.  If,  when  this  effect  has  been  produced,  the  divided 


Fio.  160. — Effect  upon  smallest  arteries  of  posterior  extremity  of  exciting  peripheral  trunk  of  left 
sciatic  in  horse.  (Morat.)  A,f,  d,  pressure  in  central  trunk  of  right  femoral  artery  ;  A,f,  s, 
pressure  in  peripheral  trunk  of  left  femoral  artery.  Two  electric  signals  record  the  time 
in  seconds,  and  the  duration  of  excitation  by  a  tetanising  current  on  the  abscissa.  Shows 
that  the  constriction  of  the  small  arteries  of  a  posterior  limb  hardly  increases  the  central 
pressure  in  the  femoral  of  the  other  limb,  while  the  peripheral  pressure  in  the  femoral 
of  the  same  side,  which  anastomoses  with  the  small  contracting  arteries,  is  conspicuously 
increased. 

sciatic  is  again  exposed  and  excited  mechanically  at  the  peripheral 
end,  the  temperature  of  the  paw  rises  considerably  and  exceeds 
that  of  the  normal  side.  This  shows  the  presence  of  dilator  fibres 
in  the  sciatic,  which  retain  their  excitability  for  a  longer  time 
after  section  than  the  vaso-constrictors.  These  results  of  Goltz 
were  essentially  confirmed  by  the  subsequent  observations  of 
Ostroumoff,  Heidenhain  and  Griitzner,  Kendall  and  Luchsinger, 
and  others. 

In  1876  v.  Frey  in  Ludwig's  laboratory  took  up  Cl.  Bernard's 
studies  on  the  vascular  nerves  of  the  subniaxillary  gland,  and 
determined  the  amount  of  blood  which  flows  out  of  the  chief  vein 
of  the  glands  in  the  time-unit,  when  the  dilators  in  the  chorda 
tympani,  or  the  constrictors  of  the  carotid  branches  of  the 
sympathetic,  are  separately  stimulated;  or,  lastly,  when  both 
kinds  of  nerves  are  excited  simultaneously.  The  separate  stimu- 
lation of  the  two  nerves  showed  that  the  dilators  have  a  much 


352 


PHYSIOLOGY 


CHAP. 


longer  after-effect,  and  are  more  quickly  tired  than  the  constrictors. 
Simultaneous  stimulation  showed  the  functional  predominance  of 
the  constrictors  over  the  dilators,  of  which,  however,  the  excitation 
is  manifested  by  an  after-effect — in  agreement  with  Baxt's 
experiments  on  the  cardiac  nerves.  When,  on  the  contrary,  the 
constrictors  are  stimulated  with  a  weak,  and  the  dilators  with  a 
strong,  current,  the  latter  predominate. 

Certain  experiments  of  Lepine,  and   later  on  of  Bernstein, 


FIG.  161.— Plethysmograrn.s  of  hind-limb  of  cat  during  electrical  excitation  of  divided  sciatic, 
by  induction  shocks  of  varying  frequency.  (Bowditch  and  Warren.)  The  sciatic  was  excited 
in  the  intervals  comprised  between  the  two  vertical  lines  =  15".  At  A,  with  1  shock  at  each 
second,  a  slight  vascular  contraction,  followed  by  marked  dilatation,  was  obtained.  At  B,  with 
4  shocks  at  each  second,  the  contraction  was  larger,  with  a  larger  succeeding  vascular 
dilatation.  At  C,  with  16  shocks  per  second,  there  was  marked  contraction  with  very  small 
dilatation.  At  D,  with  64  shocks  per  second,  there  was  a  very  marked  contraction,  with  no 
subsequent  vascular  dilatation. 

indicate  that  the  atonic  or  hypertonic  state  of  the  vessels  previous 
to  electrical  excitation  of  their  respective  nerves  leads  to  the 
preponderance  of  the  constrictors  over  the  dilators,  and  vice  versa. 
They  found,  namely,  that  the  stimulation  of  the  sciatic  produced 
constriction  or  dilatation  of  the  vessels,  according  as  the  extremities 
had  previously  been  warmed  or  cooled  with  hot  or  cold  water. 

Ostroumoff  further   showed   that   a   different   rhythm,   or  a 
varying  intensity  of  electrical  excitation,  led  to  the  predominance 


x  VASCULAK  MUSCLE  AND  NERVES  353 

of  one  or  other  kind  of  vascular  nerve.  The  dilators  are  more 
readily  excitable  to  currents  of  slow  rhythm  or  low  intensity ; 
the  constrictors,  on  the  other  hand,  to  tetanising  currents,  i.e. 
currents  of  high  frequency,  or  great  intensity.  These  results 
were  strikingly  developed  and  confirmed  in  the  experiments  of 
Bowditch  and  Warren  on  the  cat  by  the  plethysmograph  method, 
in  which  the  oscillations  of  volume  in  the  hind -limbs  were 
recorded  during  the  excitation  of  the  sciatic  by  currents  of  high 
or  low  frequency  and  intensity.  The  plethysniograms  of  Figs.  161 
and  162  are  so  plain  as  to  need  no  description. 

On  the  other  hand,  Piotrowski  was  unable  on  the  dog  to  obtain 
the  same  results  as  Bowditch  and  Warren.  On  stimulating  the 
sciatic  with  varying  frequencies,  he  constantly  observed  a  diminu- 
tion and  never  an  increase  in  the  volume  of  the  limb. 

The  two  kinds  of  vascular  nerves,  which  run  together  in  the 
peripheral  nervous  system,  may  take  a  separate  course  at  a  higher 
point  and  leave  the  cord  at  different  places.  This  was  shown  by 


Fiu.  162. — Plethysmograms  of  hind-limb  of  cat  during  electrical  excitation  of  divided  sciatic,  by 
induction  shocks  of  equal  frequency  (1  per  second),  and  equal  duration  (20"),  but  of  varying 
strength.  (Bowditch  and  Warren.)  At  A,  with  strength  of  shock  =  100,  primary  dilatation  of 
vessels  of  limb;  at  B,  with  strength  of  shock  =  150,  more  pronounced  dilatation  preceded  by 
temporary  contraction;  at  C,  with  strength  of  shock ^200,  still  more  marked  dilatation, 
preceded  by  greater  vascular  constriction. 

Dastre  and  Morat,  who,  on  exciting  the  thoracic  sympathetic 
immediately  above  the  diaphragm,  constantly  obtained  dilatation 
of  the  vessels  in  the  lower  limbs,  while  on  exciting  the  abdominal 
sympathetic  or  sciatic  they  were  constricted. 

Yet  more  interesting  is  another,  fact  discovered  by  the  same 
authors,  which  plainly  shows  that  the  two  kinds  of  vascular  nerves, 
running  in  a  single  nerve  trunk,  may  supply  quite  distinct  regions 
at  the  periphery.  On  repeating  the  stimulation  of  the  cervical 
sympathetic  (which  forms  with  the  vagus  a  single  trunk,  known  as 
the  vago-sympathetic)  on  a  curarised  dog,  they  observed  blanching 
in  the  skin  of  the  ear  and  mucosa  of  the  tongue,  epiglottis,  tonsils, 
and  soft  palate  on  the  side  excited,  with  the  simultaneous  flushing 
of  the  mucosa  of  the  lips,  gums,  cheeks,  hard  palate,  and  nasal 
mucosa  on  the  same  side.  The  effect  is  particularly  striking  on 
comparison  with  the  other  side,  and  -on  contrasting  the  ischaemic 
and  hyperaemic  parts.  At  the  close  of  excitation  the  differences 
gradually  disappear,  until  the  several  parts  regain  their  normal 
colouring.  The  entire  effect  is  due  to  the  sympathetic  alone,  and 
not  to  the  vagus,  since  it  appears  when  the  sympathetic  is  excited 

VOL.  I  2  A 


354  PHYSIOLOGY  CHAP. 

above  or  below  its  union  with  the  vagus,  or  when  the  latter  has 
been  divided  above  the  point  of  junction. 

It  thus  appears  that  while  the  vaso-dilators  almost  always  run 
with  the  vaso-constrictors,  their  presence  in  the  several  nerve- trunks 
can  be  detected,  either  by  the  physiologically  distinct  character  of 
their  activity,  or  by  their  different  course,  their  central  origin, 
and  their  morphologically  distinct  peripheral  distribution. 

The  data  at  present  before  us  in  regard  to  the  course  and 
central  origin  of  the  vaso-dilators  to  the  different  regions  are  less 
complete  than  those  relating  to  the  vaso-constrictors. 

The  dilators  contained  in  the  cervical  sympathetic  were  traced 
by  Dastre  and  Morat  into  the  two  branches  of  the  Annulus  of 
Vieussens,  the  rami  communicantes  to  the  second  to  fifth  spinal 
nerves,  and  the  anterior  roots  of  the  same.  The  majority  unite  on 
their  way  to  the  periphery  with  the  trigeniinal,  by  an  anastomosis 
between  the  superior  cervical  and  Gasserian  ganglions.  For  after 
section  of  the  first  branch  of  the  trigeniinal  in  the  pterygoid- 
inaxillary  groove,  the  vascular  dilatation  resulting  from,  stimulation 
of  the  cervical  sympathetic  appears  only  to  a  minimal  degree  in 
the  regions  above  indicated.  On  the  other  hand,  with  excitation 
of  the  trigeminal,  after  division  and  degeneration  of  the  cervical 
sympathetic,  dilatation  of  the  facial  vessels  is  obtained.  This 
shows  that  the  dilator  fibres  of  this  nerve  cannot  all  emerge  by 
the  sympathetic  and  be  of  spinal  origin ;  others  accompany  the 
trigeminus  from  its  roots  and  are  cerebral  in  origin.  According 
to  Carlson  (1907)  the  cervical  sympathetic  carries  both  vaso- 
dilators and  vaso-constrictors  to  the  cat's  submaxillary  gland. 
This  fact  had  been  overlooked  by  preceding  investigators  (Heiden- 
hain,  Langley,  Bayliss),  who  speak  only  of  vaso-constrictor  fibres  to 
the  salivary  gland  in  the  cervical  sympathetic.  This  is  due  to 
their  observations  having  been  made  upon  the  dog  (and  other 
mammals),  in  which  the  constrictors  probably  preponderate  in  the 
cervical  sympathetic,  so  that  on  stimulating  the  nerve  the 
constrictor  effect  alone  is  apparent. 

According  to  Langley,  the  dilators  of  the  fore-limb  originate  in 
the  thoracic  nerves  (5th-8th  pairs).  The  greater  proportion  of  the 
dilators  to  the  hind-limbs  run  in  the  sciatic,  a  very  few  in  the 
crural.  The  work  of  Ostrournoff  and  others  shows  that  these  do 
not  arise  in  the  sacral,  but  in  the  lumbar  roots  (2nd-4th  pairs), 
passing  thence  by  the  rami  communicantes  to  the  abdominal 
sympathetic  (and  in  a  minority  to  the  thoracic  sympathetic)  before 
they  unite  with  the  sciatic.  According  to  the  observations  of 
Strieker,  subsequently  confirmed  by  Cossy,  Vulpian,  and  others, 
they  do  not  arise  like  all  other  motor  nerves  in  the  anterior  roots 
alone,  but  also  in  the  posterior  roots  of  the  fourth  to  fifth  lumbar 
pairs.  This  is  the  only  well-proved  exception  to  Bell's  law  (see 
vol.  iii.). 


x  VASCULAR  MUSCLE  AND  NERVES  355 

The  recent  work  of  Bayliss  (1901)  on  the  origin  of  the  vaso- 
dilator nerves  has  confirmed  and  completed  Strieker's  observations, 
although  it  is  partly  contradictory  of  the  conclusions  just 
enumerated.  Electrical,  chemical,  thermal,  and  above  all  mechanical 
stimulation  of  the  peripheral  trunk  of  the  divided  posterior  roots 
of  the  fifth,  sixth,  and  seventh  lumbar,  and  the  first  sacral  nerves, 
determine  on  the  dog  a  pronounced  vaso-dilatation  of  the  hind- 
limb.  A  similar  dilatation  of  the  fore-limb  is  exhibited  on 
stimulating  the  posterior  roots  of  the  sixth,  seventh,  and  eighth 
cervical  and  first  thoracic  nerves.  The  dilator  fibres  of  the  hind- 
limbs  do  not  run  with  the  abdominal  sympathetic,  but  enter  the 
lumbo-sacral  plexus  direct.  They  degenerate  after  extirpation  of 
the  spinal  ganglia,  but  do  not  degenerate  when  the  posterior  roots 
are  cut  between  the  cord  and  the  spinal  ganglia.  They  thus 
behave  in  a  manner  perfectly  analogous  to  all  other  nerve-fibres 
emerging  from  the  posterior  roots,  which  have  their  trophic  centres 
in  the  spinal  ganglia.  Lastly,  it  has  not  been  demonstrated  that 
the  hind-limbs  receive  any  vaso-dilator  fibres  other  than  those 
which  run  in  the  posterior  spinal  roots. 

Till  quite  recently  little  was  known  of  the  dilator  fibres  to  the 
visceral  vessels.  Bradford,  on  methodically  stimulating  the  several 
pairs  of  spinal  nerves  with  low  frequency  currents,  found  that  the 
eleventh,  twelfth,  and  thirteenth  dorsal  pairs  at  least,  in  addition 
to  the  constrictor  fibres,  contain  numerous  dilator  fibres  to  the 
renal  vessels,  these  being,  on  the  contrary,  very  few  in  the  other 
dorsal  pairs,  and  altogether  absent  in  the  lumbar  pairs.  On 
experimenting  by  the  same  method  with  the  splanchnic,  the  most 
important  of  the  vaso-constrictor  nerves,  he  found  that  it  also 
contains  vaso-dilator  fibres,  which  probably  serve  the  intestines. 

After  Eckhard's  discovery  of  the  nervi  erigentes  (1863)  they 
were  at  a  later  period  studied  by  Gaskell  (1887)  and  Morat  (1890), 
with  the  object  more  particularly  of  determining  their  origin.  It 
was  found  that  stimulation  of  the  anterior  roots  of  the  second  and 
third  sacral  nerves  in  rabbit,  and  first  and  second  sacral  nerves  in 
the  dog,  caused  almost  as  pronounced  an  erection  of  the  penis 
as  the  stimulation  of  the  nervi  erigentes.  Stimulation  of  the 
posterior  roots  never  produces  the  slightest  trace  of  erection. 

These  are  the  most  important  experimental  data  in  regard  to 
the  origin  and  course  of  the  vaso- dilators. 

V.  The  vascular  nerves,  like  the  cardiac  nerves,  are  capable  of 
reflex  excitation,  i.e.  they  can  be  stimulated  by  the  afferent  nerves 
to  the  centres.  As  in  the  heart  there  are  afferent  nerves  which 
act  reflexly  upon  the  heart  itself,  -so  in  the  vessels  we  must 
assume  the  existence  of  afferent  nerves,  capable  of  acting  reflexly 
on  the  vessels.  This  was  first  demonstrated  by  Heger  (1887).  In 
the  curarised  dog  or  rabbit  he  injected  nicotine  or  silver  nitrate, 
peripherally,  by  the  crural  artery,  and  simultaneously  recorded  the 


356  PHYSIOLOGY  CHAP. 

lateral  pressure  of  the  aorta  after  ligaturing  the  crural  vein. 
Directly  after  the  injection  he  observed  either  an  instantaneous 
fall  of  blood  pressure,  or  a  fall  preceded  by  a  rise.  Heger  referred 
this  reflex  phenomenon  to  the  action  of  the  capillary  walls,  since 
neither  pressor  nor  depressor  effects  appeared,  when  the  injected 
substance  was  localised  in  the  artery  or  vein.  The  reflex  also 
occurs  when  the  hind-limb  is  only  connected  by  the  sciatic  to  the 
rest  of  the  body. 

Spallitta  and  Consiglio,  in  Marcacci's  laboratory,  extended  and 
completed  the  observations  of  Heger.  According  to  the  Italian 
workers,  excitation  of  the  sensory  nerves  to  the  internal  surface 
of  the  blood-vessels,  by  chemical  agents,  constantly  produces  not 
merely  rise  of  blood  pressure,  but  also  slowing  of  heart-beat  with 
increased  amplitude  of  pulse.  Since  excitation  of  the  sensory 
nerves  of  the  heart,  or,  according  to  the  latest  researches,  of  the 
aorta,  produces  a  depressor  effect,  antagonistic,  i.e.  to  that  of  the 
afferent  nerves  to  the  peripheral  vessels,  it  seems  logical  to  conclude 
that  under  normal  conditions  also  the  two  kinds  of  sensory  nerves 
exert  an  opposite  action  on  the  circulation.  The  sensory  nerves  of 
the  heart  or  aorta  prevent  undue  filling  or  overloading  of  the 
heart ;  the  sensory  nerves  of  the  peripheral  vessels  obviate  undue 
filling  and  distension  of  the  vessels. 

Since  it  is  proved  that  vascular  reflexes  may  be  excited  by 
afferent  fibres  in  the  walls  of  the  vessels  themselves,  it  is  probable 
that  they  play  a  part  in  the  physiological  regulation  of  blood 
pressure.  On  the  other  hand,  the  tone  of  the  vessels  can  be 
reflexly  influenced  by  any  centripetal  nerve.  Localised  vascular 
reflexes  usually  cause  the  vessels  to  widen,  but  at  other  times 
they  are  first  narrowed,  and  subsequently,  as  an  after-effect, 
become  wider.  This  means  that  the  stimulation  of  the  afferent 
nerves  is  transmitted  either  by  the  vaso-dilators,  or  by  the  vaso- 
constrictors, or  lastly,  by  both  kinds  of  nerves.  The  inconstant  or 
totally  negative  results  of  a  number  of  experiments  find  their 
probable  explanation  in  the  partial  or  total  inhibition  of  the  effect. 
Only  a  few  examples  can  here  be  cited. 

If  the  nerves  of  taste  are  excited  by  sapid  substances,  there  is 
not  only  a  reflex  secretion  of  saliva,  but  also  a  marked  dilatation 
of  the  vessels  innervated  by  the  chorda  tympani  (Claude  Bernard). 
Central  excitation  of  the  posterior  auricular  nerve  usually  produces 
dilatation  of  the  vessels  of  the  rabbit's  ear ;  often,  however,  this  is 
preceded  or  followed  by  vaso-constriction  (Snellen  and  Loven). 
On  stimulating  the  nerve  in  the  dorsuni  of  the  dog's  paw,  dilata- 
tion of  the  saphenous  artery  is  obtained;  on  exciting  the  infra- 
orbital,  or  mental  (labial)  nerve,  there  is  dilatation  of  the  external 
maxillary  artery  (Loven).  Central  excitation  of  the  sciatic, 
the  vagus,  or  the  posterior  spinal  roots,  usually  produces 
reflex  constriction  of  the  kidney  vessels ;  on  the  other  hand, 


x  VASCULAK  MUSCLE  AND  NERVES  357 

dilatation  of  the  same  vessels  is  obtained  when  the  posterior  roots 
of  the  eleventh  and  twelfth  dorsal  nerves  are  stimulated,  because 
in  that  case  the  excitation  is  conveyed  by  the  anterior  roots  of 
the  same,  which,  as  we  have  seen,  contain  dilator  fibres  (Bradford). 

The  vascular  reflexes  may  extend  from  one  side  to  the  other  of 
the  body.  On  central  excitation  of  the  sciatic,  the  paw  on  the 
opposite  side  becomes  warmer  (Masius  and  Yanlair) ;  stimulation 
of  the  nasal  mucosa  dilates  the  vessels  of  the  whole  head,  but  more 
decidedly  on  the  excited  side  (Fram;ois-Franck). 

The  vascular  reflexes  in  man  have  also  been  investigated. 
When  one  hand  is  dipped  into  cold  water,  the  vessels  of  the  other 
hand  contract  (Brown-Sequard).  On  electrical  excitation  of  one 
limb  the  vessels  of  the  opposite  side  contract  (Maragliano). 


FIG.  1 63.  —  Plethysmograms  of  hand  (M)  and  foot  (P)  recorded  from  healthy  subject  in  re- 
cumbent and  motionless  posture.  (Fano.)  The  abscissa  S,  traced  with  a  Deprex  signal,  in- 
dicates at  E  the  moment  of  electrical  excitation  of  the  skin.  The  line  D  is  traced  by  a 
tuning-fork  vibrating  at  10  vibrations  per  second. 

Fano  has  also  experimented  on  the  vascular  reflexes  of  man, 
using  an  air  plethysmograph,  by  which  he  was  able  to  record 
simultaneously  the  pulse  and  the  changes  in  volume  of  the  hand 
and  foot.  He  came  to  the  following  conclusions  :  the  reaction 
time  of  the  vessels  is  always  very  long ;  it  oscillates  between  two 
and  seven  seconds,  according  to  the  conditions  in  which  .the  subject 
of  the  experiment  is  placed,  and  the  part  of  the  body  stimulated. 
The  vascular  constriction  consequent  on  a  stimulus  is  always  more 
pronounced  in  sleep  than  in  waking.  The  reaction  time  is  longer 
in  sleep  than  in  waking.  The  reaction  always  occurs,  inde- 
pendent of  the  point  of  stimulation,  first  in  the  upper  and  then 
in  the  lower  extremities.  In  the  latter,  however,  the  constriction 
is  more  persistent  (Fig.  163). 


358 


PHYSIOLOGY 


CHAP. 


Patrizi  instituted  numerous  plethysmographic  researches  with 
the  object  of  determining  the  exact  vasomotor  reflex  tissues  in  the 
arms,  legs,  and  brain  of  man,  when  awake,  when  asleep,  and  undei" 
various  other  conditions.  Besides  confirming  certain  general  laws 
for  reflexes,  in  the  vascular  regions,  Patrizi  found  that  the  vascular 
reflex  times,  which  are  fairly  equal  in  the  waking  state,  for  the  arms 
and  legs,  with  a  slight  advantage  on  the  side  of  the  upper  limbs, 
undergo  in  the  latter  a  considerable  delay  in  sleep,  whereas  the  reflex 
time  for  the  lower  limbs  remains  constant.  During  sleep  the 
reflexes  are  most  delayed  in  the  cerebral  vessels. 

Patrizi   and   Cavani  also  detected  a  right-   and    left-handed 


FIG.  164. — Reflex  pressure  effect  on  excitation  of  rabbit's  skin  at  E.  (Tigerstedt.)  Carotid  con- 
nected with  Ludwig's  kymograph.  Time  tracing  from  an  electric  signal,  along  the  abscissa, 
in  seconds. 

vasomotor  asymmetry  in  man,  to  which  they  attributed  a  more 
rapid  and  pronounced  vasomotor  reaction,  in  one  as  against  the 
other  half  of  the  body. 

This  superiority  of  vasomotor  functions  usually  obtains  in  that 
half  of  the  body  which  shows  itself  most  capable  of  muscular  force. 
The  time  gained  in  the  vascular  reflexes  in  the  favoured  half  of 
the  body  may  amount  almost  to  one  second. 

In  all  probability  the  vasomotor  asymmetry  is  due  to  the 
greater  permeability  of  the  nerve  paths  in  the  better  exercised  limb, 
which  does  not  exclude  the  possible  influence  of  the  varying 
sensory  excitability  in  the  two  halves  of  the  body,  and  in  the  two 
corresponding  sides  of  the  brain. 

These  reflexes  not  infrequently  occur  in  the  vascular  regions 


x  VASCULAR  MUSCLE  AND  NERVES  359 

most  remote  from  the  afferent  nerves  stimulated.  The  visceral 
vessels  innervated  by  the  splanchnic  readily  respond  to  the  reflex 
action  of  any  sensory  nerve,  for  the  most  part  by  contracting, 
sometimes  by  dilating,  Stimulation  of  the  sciatic  also  constricts 
the  vessels  of  the  tongue  (Vulpian) ;  excitation  of  the  brachial 
nerve  dilates  the  vessels  of  the  ear  (Loven).  This  last  effect  may 
be  seen  on  the  rabbit,  whatever  the  sensory  nerve  stimulated,  but 
the  dilatation  is  usually  preceded  by  vaso-constriction  (Eckhard). 
•  When  the  vascular  reflexes  are  not  confined  to  any  circum- 
scribed area,  but  extend  to  a  wider  region,  they  cause  a  general 


FIG.  165.— Reflex  lowering  of  arterial  pressure,  from  electrical  excitation  of  depressor 
nerve  of  rabbit,  in  period  comprised  between  two  vertical  lines.    (Tigerstedt.) 

modification  in  blood  pressure,  usually  expressed  in  an  abnormal 
rise,  sometimes  in  a  fall  of  pressure. 

The  reflex  pressor  effects  of  exciting  the  sensory  nerves,  already 
noted  by  Magendie,  were  clearly  worked  out  for  the  first  time  by 
von  Bezold  (1863),  and  were  subsequently  extended  by  a  number 
of  other  experimenters. 

They  follow  particularly  on  the  stimulation  of  the  posterior 
spinal  roots,  the  vagus,  the  trigeminus,  the  sciatic,  the  greater  and 
lesser  splanchnic,  the  cutaneous  and  muscular  nerves,  the  nerves  of 
the  special  senses  (Fig.  164).  The  rise  of  blood  pressure  varies  with 
the  nerve  excited,  and  also  with  the  intensity  and  nature  of  the 
stimulus.  The  state  of  the  animal  prior  to  stimulation  also  has 
great  influence  on  the  intensity  of  the  pressor  effect.  In  the 
normal  animal,  e.g.,  acoustic  stimuli  induce  a  considerable  rise  of 


360 


PHYSIOLOGY 


CHAP. 


arterial  pressure,  which  varies  with  the  pitch,  strength,  and  timbre 
of  the  sound,  whereas  in  curarised  animals  the  rise  is  hardly 
perceptible  (Dogiel).  Lastly,  both  the  number  of  sensory  nerves, 
and  the  extent  of  the  area  stimulated,  have  great  influence  on  the 
degree  of  pressor  effect.  For  instance,  on  exciting  a  limited  area 
of  the  skin  with  strong  chemical  stimuli,  with  boiling  water,  or 
red-hot  iron,  little  or  no  rise  of  pressure  is  obtained ;  on  the  other 
hand,  slight  contact,  tickling,  or  blowing  of  extended  areas  of  the 
skin,  raises  the  arterial  pressure  to  nearly  double  the  normal 
(Heidenhain  and  Griitzner). 

We  saw  in  the  preceding  chapter  that  the  central  excitation  of 
the  depressor  nerves  of  Ludwig  and  Cyon  invariably  produces  a 


Fir..  106.— Reflex  lowering  of  arterial  pressure  of  rabbit,  from  electrical  excitation  of 
centripetal  muscular  nerve,  in  period  comprised  by  vertical  lines.     (Tigerstedt.) 

marked  reflex  fall  of  arterial  pressure  (Fig.  165).  The  afferent 
nerves  to  the  muscles  also  constantly  produce  a  similar  effect  on 
blood  pressure  (Fig.  166). 

Few  other  afferent  nerves  are  capable  of  producing  reflex 
depressor  effects.  The  glosso-pharyngeal  usually,  but  not  invariably, 
lowers  blood  pressure  (Knoll).  With  mechanical  stimulation  of 
the  rectal  and  vaginal  rnucosa,  especially  on  touching  the  anus 
and  vaginal  orifice,  a  primary  fall  of  aortic  pressure  may  be 
observed  on  the  curarised  dog  (Belfield).  But  if  the  stimulation 
of  the  inucosa  is  pushed  to  deeper  parts,  the  depression  is  less, 
and  may  even  be  replaced  by  a  pressor  effect.  Mechanical  stimula- 
tion of  the  skeletal  muscles,  again,  may  produce  a  depressor  effect 
(Kleen). 

We  saw  that  the  fall  of  arterial  pressure  consequent  on  excita- 
tion of  the  depressors  is  due  principally  to  the  vaso-dilator  fibres 


x  VASCULAK  MUSCLE  AND  NEKVES  361 

of  the  splanchnic  nerve,  partly  to  other  dilator  nerves,  since,  when 
the  splanchnics  are  divided,  the  depressor  part  is  not  entirely 
abolished.  It  has,  however,  been  established  that  the  depressors 
do  not  exert  their  reflex  dilator  action  upon  all  the  vascular  regions, 
and  that  the  vessels  of  the  ear,  face,  adjacent  mucosae,  and  perhaps 
of  the  skin  in  general,  are  constricted  during  stimulation  of  the 
depressors  (Dastre  and  Morat). 

The  reflex  pressor  effects  on  excitation  of  the  sensory  nerves  are 
chiefly  due  to  the  vaso-constrictor  fibres  of  the  splanchnics,  because 
when  these  nerves  are  divided,  they  are  much  reduced.  But  even 
in  these  cases  vaso-constriction  is  not  the  only  reflex  effect,  since 
it  can  be  shown  that  while  the  internal  visceral  vessels  contract, 
the  cutaneous  vessels  dilate.  This  fact,  which  indicates  a  certain 
antagonism  between  the  deep  and  the  superficial  vessels  of  the 
body,  was  demonstrated  by  Heidenhain  in  measurements  of  the 
temperature  of  the  skin  and  of  the  deep-lying  portions  of  the  body 
during  excitation  of  the  sensory  nerves. 

The  antagonism  between  the  cutaneous  and  visceral  vessels 
is  even  more  apparent  in  the  asphyxia  produced  by  suspension  of 
artificial  respiration  in  curarised  animals.  While  the  cutaneous 
vessels  of  ear,  face,  and  extremities  dilate,  those  of  the  viscera 
(intestine,  spleen,  kidneys,  uterus)  contract.  The  pressure  effect 
results  from  the  predominance  of  vaso-constriction  in  the  visceral 
vessels  over  dilatation  of  the  superficial  vessels  (Dastre  and  Morat). 
It  is  highly  probable,  although  definite  experimental  evidence 
is  wanting,  that  this  dilatation  is  active,  and  not  the  passive  effect 
of  the  constriction  of  the  deep  vessels. 

We  must  not,  however,  take  this  supposed  antagonism  between 
the  deep  and  the  superficial  vessels  in  too  absolute  a  sense,  since 
the  fact  that  in  vascular  reflexes  constriction  of  the  one  and 
dilatation  of  the  other  occurs  is  not  constant.  Heidenhain, 
indeed,  observed  with  strong  electrical  excitation  of  the  medulla 
oblongata  that  there  was  a  pressor  effect  greater  than  that  of 
asphyxia  or  any  kind  of  reflex  stimulation,  which  was  determined 
not  merely  by  constriction  of  the  internal  vessels,  but  by  that  of 
the  cutaneous  and  muscular  vessels  also. 

VI.  The  vascular  reflexes,  i.e.  the  excitatory  processes  trans- 
mitted from  the  centripetal  or  afferent  to  the  centrifugal  or 
efferent  nerves  (the  constrictors  or  dilators  of  the  vessels),  are 
necessarily  carried  out  by  means  of  the  centres  in  the  cerebro- 
spinal  system,  from  which  the  vascular  nerves  arise.  The  capacity 
of  the  peripheral  ganglia  of  the  sympathetic  system  to  function 
as  centres  for  reflex  processes  (in  so  far  as  reflex  is  taken  in 
the  restricted  sense  of  a  transformation  of  afferent  into  efferent 
influences)  has  not  yet  been  demonstrated,  even  if  it  cannot  be 
a  priori  excluded. 

We  have  seen  that  the  greater  part,  if  not  the  whole,  of  the 


362  PHYSIOLOGY  CHAP. 

vaso-constrictor  fibres  arise  from  the  anterior  roots  of  the  nerves 
in  the  median  or  thoracic  section  of  the  cord,  which  is  therefore 
the  principal  seat  of  the  apparent  origin  of  these  fibres.  Next 
arises  the  question  as  to  the  centres,  i.e.  the  real  origins  of  the 
same.  Other  special  questions  are  associated  with  these.  Is 
there  in  the  central  nervous  system  one  single  vasomotor  centre, 
or  are  there  several  centres  ?  If  several,  are  they  unified  in  their 
functions,  and  associated  so  as  to  form  one  single  system,  or  can 
they  function  independently  one  of  another?  Are  there  con- 
trolling centres  of  general  circulation  on  which  the  tone  of  the 
whole  vascular  system  depends,  and  controlling  centres  of  local 
circulation,  on  which  the  vascular  tone  of  this  or  that  organ  or 
tissue  depends  ?  Generally  speaking,  it  must  be  admitted  that  we 
are  not  yet  in  a  position  to  give  a  clear  and  exhaustive  answer 
to  these  different  questions,  particularly  to  that  of  the  precise 
localisation  of  the  vascular  centres.  We  must  confine  ourselves 
to  the  more  fundamental  and  better  established  data,  and  to 
drawing  from  these  such  conclusions  as  are  legitimate  in  the 
present  state  of  our  knowledge. 

As  early  as  1855,  shortly  after  the  discovery  of  the  vaso- 
constrictors, M.  Schiff  suggested,  in  view  of  the  effects  of 
transversely  dividing  the  cord  at  different  heights,  that  these 
nerves  might  have  their  centre  in  the  bulb  or  medulla  oblongata. 
In  1859  Cl.  Bernard  observed  a  considerable  fall  in  blood  pressure 
after  division  of  the  cervical  cord,  but  he  did  not  pursue  the 
subject,  and  von  Bezold  next  took  it  up  in  1863.  He  found  in 
curarised  animals  that  stimulation  of  the  cervical  cord  produced 
such  an  increase  in  arterial  pressure  that  it  becomes  seven  times 
greater  than  it  was  immediately  after  section  of  the  cord.  This 
marked  rise  of  pressure,  which  was  associated  with  a  pronounced 
acceleration  of  cardiac  rhythm,  was  referred  by  him  to  increased 
activity  of  the  heart,  without  taking  into  consideration  the  inter- 
vention of  vascular  nerves. 

A  year  after  the  publication  of  von  Bezold's  theory,  Ludwig 
and  Thiry  showed  it  to  be  erroneous,  emphasising  the  fact  that 
during  excitation  of  the  cervical  cord  the  small  arteries  throughout 
almost  the  entire  body  are  constricted,  which  causes  the  pressor 
effect.  For,  on  exciting  the  cervical  cord,  a  maximal  rise  of  aortic 
pressure  is  obtained,  even  after  the  whole  of  the  cardiac  nerves 
have  been  divided.  The  fall  after  section  is  therefore  the  effect 
of  paralytic  atony  of  the  vessels;  the  rise  of  pressure  during 
excitation  is  the  effect  of  vascular  hypertony  ;  there  must  therefore 
exist  in  the  bulb,  i.e.  above  the  divided  and  excited  cord,  a  vaso- 
constrictor centre,  which  exerts  a  constant  tonic  action  upon  all 
the  small  arteries. 

Contemporaneously  with  Ludwig  and  Thiry,  Goltz,  by  certain 
experiments  on  the  frog,  showed  the  importance  of  vascular  tone 


x  VASCULAR  MUSCLE  AND  NERVES  363 

to  the  circulation.  After  destruction  of  the  central  nervous 
system,  there  is  a  marked  dilatation  of  the  visceral  vessels, 
particularly  of  the  veins,  in  consequence  of  which  nearly  the 
whole  of  the  blood  collects  in  those  vessels,  while  the  remaining 
parts  of  the  body  are  much  impoverished.  On  exposing  the 
beating  heart,  he  saw  that  it  was  almost  bloodless,  since  very  little 
blood  reached  it  during  diastole,  and  therefore  very  little  could  be 
expelled  into  the  aorta  during  systole.  It  follows  that  vascular 
tonicity  is  an  indispensable  condition  of  the  circulation,  and  that 
not  merely  the  arteries,  but  the  veins  as  well,  possess  a  tone  that  is 
dependent  on  the  central  nervous  system  in  general. 

The  bulbar  centre  for  the  vaso-constrictors  was  more  exactly 
localised  and  determined  in  the  subsequent  investigations  of 
Owsjannikow  (1871)  and  Dittmar  (1873),  in  Ludwig's  laboratory. 
Starting  from  the  fact  that  central  excitation  of  the  sciatic  in 
curarised  dogs  and  rabbits,  even  after  separation  of  spinal  bulb 
from  brain  by  a  transverse  section,  reflexly  produces  a  perceptible 
increase  in  arterial  blood-pressure,  they  endeavoured  to  define  the 
region  of  the  bulb  in  which  this  reflex  occurred.  With  this 
object  Owsjannikow  made  successive  cross-sections  from  above 
downwards  at  different  heights  of  the  medulla,  and  examined  both 
the  depressor  effect  of  each  section,  and  the  reflex  pressor  effect  on 
exciting  the  sciatic.  The  upper  limit  of  the  vascular  centre  lies 
at  the  level  of  that  section  after  which .  there  is  a  fall  in  aortic 
pressure,  and  a  diminution  in  the  height  of  the  reflex  rise  of 
pressure;  the  lower  limit  is  at  that  section  after  which  aortic 
pressure  reaches  its  minimum,  and  no  longer  rises  on  excitation 
of  the  sciatic.  By  pursuing  this  method,  with  the  guidance  of 
the  above  data,  he  decided  that  the  bulbar  vasomotor  centre  in 
the  rabbit  is  about  4  mm.  high  ;  its  upper  limit  is  1-2  mm.  below 
the  corpora  quadrigemina,  its  lower  limit  4  mm.  above  the  point 
of  the  calamus  scriptorius.  Since  longitudinal  section  of  the  bulb 
in  the  median  line  produces  no  perceptible  fall  in  aortic  pressure, 
he  concludes  that  the  centre  is  not  in  the  median  line,  but  consists 
of  two  centres  situated  at  either  side  of  the  bulb. 

Dittmar,  who  practically  confirmed  the  results  of  Owsjannikow 
in  regard  to  the  longitudinal  extension  of  the  bulbar  vascular 
centre,  went  on  to  establish  its  limits  in  the  two  other  dimensions, 
by  the  same  method  of  systematic  sections.  He  discovered  that  in 
each  half  of  the  bulb  there  is  a  small  prismatic  space,  on  destroying 
which  the  reflex  vascular  constriction  is  abolished.  In  this  area 
a  nucleus  of  grey  matter  is  visible  under  the  microscope,  described 
by  Clarke  as  the  antero-lateral  nucleus,  in  the  rabbit. 

The  main  results  of  Ludwig's  pupils  were  subsequently  con- 
firmed by  Heidenhain,  Berkowitsch,  Latschenberger,  and  Deahna. 

VII.  After  Ludwig's  School  had  investigated  the  bulbar  vaso- 
constrictor centres,  and  had  shown  that  after  destroying  their. 


364  PHYSIOLOGY  CHAP. 

function  it  was  no  longer  possible  to  obtain  reflex  vaso- 
constriction  on  exciting  the  sciatic,  the  opinion  generally  held  was 
that  the  cord  contained  no  other  centre  capable  of  influencing  the  '• 
tone  of  the  vessels  independent  of  that  in  the  spinal  bulb,  and 
that  this  was  probably  the  only  true  vasomotor  centre.  Very 
soon,  however,  other  experimental  observations  came  to  light 
which  showed  the  fallacy  of  this  view,  and  led  to  the  opinion  that 
there  were  secondary  vaso- cons  trie  tor  centres  along  almost  the 
whole  of  the  cord,  which  were  able  to  function  after  the  principal 
bulbar  centre  had  been  cut  out. 

Goltz  was  the  first  to  propose  this  theory  (1864-74).  He 
found  in  the  frog  that  the  vascular  atony  was  far  from  complete 
after  extirpation  of  the  entire  brain,  including  the  bulb,  and 
became  so  only  after  destruction  of  the  spinal  cord.  He  further 
observed  iu  dogs  that  when  the  cervico-dorsal  tract  was  cut  off  by 
division  from  the  lumbo-sacral,  and  the  animal  kept  alive  until 
the  vascular  atonia  of  the  hind  -  limbs  had  disappeared,  this 
atonia  was  reproduced  on  destroying  the  lumbar  cord.  He 
concluded  that  the  restoration  of  vascular  tone  after  section  of  the 
cord  was  due  to  the  presence  of  vasomotor  centres  in  the  lumbar 
medulla. 

When  cut  off  from  the  bulb,  the  spinal  vasomotor  centres  are 
also  capable  of  reflexly  constricting  the  vessels,  and  of  raising 
arterial  pressure,  when  excited,  as  was  first  shown  by  Schlesinger 
(1874)  in  dogs  and  rabbits,  after  he  had  increased  the  excitability 
of  the  cord  by  injecting  minute  doses  of  strychnine.  This  fact 
was  subsequently  confirmed  by  many  observers. 

In  curarised  animals,  when  the  cord  is  separated  from  the 
spinal  bulb,  the  asphyxia  produced  by  cessation  of  artificial 
respiration  suffices  to  cause  vascular  constriction,  as  was  first 
demonstrated  by  Kowalewsky  and  Adamiik  (1868).  Since  this 
effect  depends  on  excitation  of  the  spinal  centres,  it  follows  that, 
after  destruction  of  the  cord,  asphyxia  no  longer  exercises  any 
pressor  action  (Schlesinger,  Luchsinger,  Konow,  and  Stenbeck). 

The  spinal  centres  for  the  vaso-constrictors  lie  not  only  in  the 
lurnbo-sacral  region  (Goltz),  but  also  in  the  dorsal  tract  (Vulpian 
and  Kabierscki).  On  the  other  hand,  they  appear  not  to  exist,  or 
to  be  very  scanty,  in  the  cervical  tract,  since  aortic  pressure  is  not 
affected  by  section  of  the  cervical  cord  at  any  height,  after  the 
bulbar  centre  has  been  cut  off  (Strieker). 

The  vaso-constrictors  in  the  bundles  of  the  cord  for  the  most 
part  run  directly,  and  only  follow  the  crossed  paths  to  a  minor 
extent  (Brown-Se'quard  and  Schiff),  as  appears  from  the  effects  of 
hemisection  of  the  cord.  They  are  chiefly  mingled  with  the 
sensory  and  motor  fibres  to  the  skeletal  muscles  which  make  up 
the  lateral  bundles  (Dittmar),  as  shown  by  the  effects  of  partial 
section  in  different  segments  of  the  cord. 


x  VASCULAR  MUSCLE  AND  NERVES  365 

Nothing  certain  is  known  about  the  anatomical  and  functional 
relations  which  exist  between  the  spinal  vasomotor  centres  and 
the  bulbar  centre.  Certain  comparative  experiments  of  Kowalewsky 
and  Adamiik,  Luchsinger,  and  others  on  the  vascular  effects  con- 
sequent on  asphyxia  in  animals  with  intact  and  others  with 
divided  cord  lead,  however,  to  the  conjecture  that  the  spinal 
vaso-constrictor  centres  are  less  excitable  than  the  bulbar  centre, 
For  in  curarised  animals,  when  the  bulb  is  cut  off  from  the  cord, 
the  rise  of  arterial  pressure  at  the  close  of  artificial  respiration 
begins  and  reaches  its  maximum,  much  later  than  in  animals 
with  intact  spinal  cord.  This  leads  to  the  view  that  the  normal 
tone  of  the  vascular  centre,  and  its  rhythmical  or  a-rhythmical, 
automatic  or  reflex  oscillations,  depend  principally,  if  not  ex- 
clusively, upon  the  bulbar  centre,  which,  in  consequence  of  its 
greater  excitability,  reacts  more  quickly  to  all  stimuli,  extrinsic  or 
intrinsic. 

Just  as  there  are  vaso-constrictor  centres  below  the  ruling 
bulbar  centre,  so  it  seems  logical  also  to  assume  the  existence  of 
vaso-constrictor  centres  above  the  bulb,  i.e.  in  the  brain.  But  the 
experiments  adduced  in  this  connection  give  no  convincing 
evidence  in  favour  of  such  a  hypothesis,  since  they  are  susceptible 
of  various  interpretations.  Excitation  of  the  cerebral  peduncles 
in  curarised  animals  is  followed  by  a  pressor  effect  (Budge) ;  on 
stabbing  the  anterior  or  posterior  corpora  quadrigemina,  vaso- 
constriction  followed  by  dilatation  is  obtained  (Eckhard) ;  if  the 
corpora  striata  or  the  internal  capsule  are  electrically  stimulated, 
there  is  rise  of  arterial  pressure  (Danilewsky  and  Strieker) ;  when 
the  cortex,  particularly  in  the  region  of  the  so-called  motor  zone, 
is  electrically  excited,  a  more  or  less  distinct  pressor  effect  ensues,, 
even  if  no  epileptic  fit  is  set  up  (Danilewsky,  Bochefontainer 
Richet,  Franqois-Franck  and  others).  These  phenomena  may  be- 
explained  in  the  sense  that  there  are  no  true  vaso-constrictor 
centres  in  the  cerebrum,  but  only  simple  nerve  paths,  which  throw 
the  bulbar  vasomotor  centres  into  activity,  like  the  afferent 
peripheral  nerves.  The  effects  of  lesions  in  these  parts,  however, 
seem  to  witness  more  than  those  of  stimulation  to  the  presence 
of  true  vaso-constrictor  centres  in  the  brain. 

After  circumscribed  extirpation  of  certain  points  upon  the 
cerebral  cortex  in  the  region  of  the  motor  zone,  a  marked  and 
fairly  protracted  rise  of  temperature  in  the  hind-limbs  has  been 
observed  (Eulenburg  and  Landois) ;  in  clinical  paralysis  from  a 
variety  of  central  lesions  the  same  effect  may  be  observed  in  the 
paralysed  limbs,  as  well  as  ecchymosis  in  different  organs,  notably 
in  the  lungs  and  joints  (Charcot  and  others). 

VIII.  We  have  fewer  data  in  regard  to  the  localisation  of  the 
vaso-dilator  centres  in  the  several  parts  of  the  central  nervous 
system.  It  seems  highly  probable,  however,  that  they  are  no  less 


366  PHYSIOLOGY  CHAP. 

widely  distributed  than  the  vaso-constrictor  centres,  and  that 
there  is  in  the  bulb,  along  with  the  controlling  centre  which 
normally  regulates  the  constriction  of  the  vessels,  another  con-'- 
trolling  centre  which  regulates  their  relaxation,  so  that  the  slow 
oscillations  of  vascular  tonicity  should  be  regarded  as  the  effects  of 
the  alternating  functional  predominance  of  one  or  other  of  the 
two  opposing  bulbar  vasomotor  centres.  The  few  data  relating  to 
this  subject  may  be  briefly  summarised. 

The  rapid  and  infallible  effect  of  central  excitation  of  the 
depressor  nerves,  which  is  antagonistic  to  the  effect  consequent  on 
central  stimulation  of  the  sciatic  or  other  large  nerve  trunks,  in 
itself  makes  the  existence  of  a  controlling  vaso-dilator  centre 
highly  probable  (Ludwig  and  Cyon).  It  has  so  far  proved 
impossible  to  demonstrate  that  it  is  situated  in  the  medulla. 
Certain  experiments  of  Laffont  (1880)  are,  however,  of  interest  in 
this  connection.  He  observed  as  the  effect  of  puncturing  the 
floor  of  the  fourth  ventricle,  an  active  dilatation  of  the  hepatic 
vessels,  which  would  therefore  seem  to  depend  not  on  the  destruc- 
tion, but  on  the  stimulation  of  the  centre.  On  the  following  day 
stimulation  of  the  depressors  in  the  same  animal  failed  to  produce 
the  customary  fall  of  blood  pressure,  probably  in  consequence  of 
paralysis  due  to  the  after-effects  of  the  puncture  in  the  bulbar 
vaso-dilator  centre. 

The  following  experimental  results  prove  the  existence  of 
vaso-dilator  centres  in  the  cord  as  well.  In  dogs  that  have 
survived  transverse  division  of  the  spinal  cord  at  the  level  of  the 
last  dorsal  vertebra,  mechanical  stimulation  of  the  penis  is  able  to 
evoke  erection.  After  destruction  of  the  lumbar  cord  this  effect 
is  abolished  (Goltz).  In  the  same  dog,  with  divided  cord,  the 
central  excitation  of  one  sciatic  produces  active  dilatation  of  the 
paw  on  the  opposite  side  (Goltz,  Masius  and  Vanlair,  Ustimowitsch 
and  others).  When  the  cervical  cord  is  excited,  aortic  pressure 
falls  (Johannson) ;  there  is  dilatation  of  the  vessels  of  the  ears, 
cheeks,  and  corresponding  mucosa  (Dastre  and  Morat);  of  the 
vessels  of  the  mesentery  and  intestinal  walls  (Vulpian);  and  of 
those  of  the  penis  (Eckhard).  After  division  of  the  cord  at  the 
level  of  the  first  or  second  dorsal  vertebrae,  central  excitation  of 
the  brachial  plexus  causes  a  fall  in  aortic  pressure  (Smirnow). 

Again,  the  existence  of  cerebral  vaso-dilator  centres  is  rendered 
probable  by  the  fact  that  electrical  stimulation  of  the  cortex  at 
certain  points,  particularly  of  the  parietal  lobe,  produces  not  a 
rise  but  a  fall  of  pressure  in  the  aorta  (Bochefontaine,  Strieker, 
Bechterew,  and  Mislawsky).  These  are  probably  the  centres 
whose  activity  causes  the  sudden  blush  that  accompanies  psychical 
emotions. 

In  1893  Bayliss,  after  describing  various  experimental  results 
on  vascular  reflexes,  put  forward  the  hypothesis  that  "  the  vaso- 


x  VASCULAK  MUSCLE  AND  NEEVES  367 

motor  centre  consists  of  a  constrictor  and  a  dilator  part,  the 
depressor  nerve  acting  in  an  inhibitory  manner  on  the  former  and 
in  an  exciting  manner  on  the  latter,  while  pressor  nerves  act  in 
an  opposite  way  on  both."  Considerable  support  is  given  to  this 
view  by  his  recent  work  (1908)  on  the  reciprocal  innervation  in 
vasomotor  reflexes.  It  appears  that  in  depressor  reflexes  there  is, 
along  with  inhibition  of  tone  in  the  vaso-constrictor  centres,  an 
excitation  of  vaso-dilator  centres.  Corresponding  effects,  although 
more  difficult  to  demonstrate,  take  place  in  the  pressor  reflexes. 
The  action  of  strychnine  upon  the  vasomotor  centres  affords  a 
strict  analogy  with  its  action  as  demonstrated  by  Sherrington  in 
the  case  of  the  reflexes  to  voluntary  muscle,  i.e.  conversion  of  the 
inhibitory  phase  of  all  vascular  reflexes  into  an  excitation.  The 
depressor  nerves  cause  a  rise  of  blood-pressure  under  full  doses  of 
the  alkaloid  by  exciting  the  constrictor  centre  with  the  same 
mechanism  that  normally  inhibits  it. 


BIBLIOGRAPHY 

In  addition  to  the  copious  information  contained  in  the  general  and  special 
treatises  referred  to  in  previous  chapters,  the  student  may  consult  _  the  following 
monographs  and  memoirs  : — 

M.  SCHIFF.     Untersuchungen  zur  Physiologic  des  Nervensystems.     Frankfurt  a. 

M.,   1855.       Lehrbuch  der  Physiol.,  I.  Jahr.,   3859.       Recueil  des  memoires 

physiologiques.     Lausanne,  1194. 

CL.  BERNARD.     Le9ons  sur  la  physiologie  du  systems  nerveux.     Paris,  1858. 
ECKHARD.     Beitrage  zur  Anat.  und  Physiol.     1863. 
LUDWIG  und  THIRY.     Sitz.  Ber.  d.  kais.  Akad.  d.  Wiss.,  1864. 
LUDWIG  und  CYON.     Ber.  d.  sachs.  Gesellsch.  d.  Wiss.,  1866. 
LOVEN.     Ber.  d.  sachs.  Gesellsch.  d.  Wiss.,  1866. 

v.  BEZOLD  und  BEVER.     Untersuchungen  aus  dem  Laborat.  in  Wiirzburg,  1867. 
BROWN-SEQUARD.     Lecons  sur  les  nerfs  vaso-moteurs.     Paris,  1872. 
Mosso.     Ber.  d.  sachs.  Gesellsch.  d.  Wiss.,  1874. 

GOLTZ.     Arch.  f.  path.  Anat.,  1864.     Arch.  f.  d.  ges.  Physiol.,  1874-75. 
VULPIAN.     Le9ons  sur  1'appareil  vaso-moteur,  1875. 
HEIDENHAIN  und  GR.UTZNER.     Arch.  f.  d.  ges.  Physiol.,  1877. 
GASKELL.     Journal  of  Anat.  and  Physiol.,  1887. 

DASTRE  et  MORAT.     Recherches  sur  le  systeme  nerveux  vaso-moteur.     Paris,  1884. 
STBIGKER.     Medicin.  Jahrbiicher,  1886. 
PATRIZI.     Arch.  ital.  de  biologic.,  xxviii.  1897. 
CAVANI.     Ibidem,  vol.  xxxix.,  1903. 
PIOTROWSKI.     Arch.  f.  d.  ges.  Physiol.,  55,  1894. 
BAYLISS.     Journal  of  Physiol.,  Bd.  26,  1901. 
ASHER.     Die    Innervation   der  Gefasse.    Ergebnisse   der   Physiologie,    I,   2.  1902. 

(Sixty-eight  memoirs  are  cited  in  this  review.) 
BAYLISS.     Die   Innervation   der   Gefasse.   Ergebnisse   der   Physiologie,   V,    1906. 

(Seventy-four  memoirs  are  cited  in  this  article,  which  is  the  continuation  of 

the  preceding.) 

Recent  English  Literature  : — 

W.  T.  PORTER  and  H.  G.  BEYER.  The  Influence  of  the  Depressor  Nerve  to  the 
Vasomotor  Centre.  Amer.  Journ.  of  Physiol.,  1901,  iv.  283-299. 

W.  M.  BAYLISS.  On  the  Origin  from  the  Spinal  Cord  of  the  Vaso-dilator  Fibres 
of  the  Hind-limb  and  on  the  Nature  of  these  Fibres.  Journ.  of  Physio!., 
1900-1901,  xxvi.  173-209. 


368  PHYSIOLOGY  CHAP,  x 

W.  HUNTER.     On  the  Presence  of  Nerve-fibres  in  the  Cerebral  Vessels.     Journ.  of 

Physiol.,  1900-1901,  xxvi.  465-469. 
W.  M.   BAYLISS.     On  the  Local  Reactions  of  the  Arterial  Wall  to  Changes  of 

Internal  Pressure.     Journ.  of  Physiol.,  1902,  xxviii.  220-231. 
S.  J.  and  CLAKA  MELTZER.     A  Study  of  the  Vasomotor  Nerves  of  the  Rabbit's 

Ear  contained  in  the  Third  Cervical  and  in  the  Cervical  Sympathetic  Nerves. 

Amer.  Journ.  of  Physiol.,  1903,  ix.  57-68. 
W.  E.  DIXON  and  T.  G.  BRODIE.     Contributions  to  the  Physiology  of  the  Lungs. 

Part  II.     On  the  Innervation  of  the   Pulmonary  Blood-vessels  ;   and  some 

Observations  on  the  Action  of  Suprarenal  Extract.     Journ.  of  Physiol.,  1904, 

xxx.  476-502. 
A.  J.  CARLSON.     Vaso-dilator  Fibres  to  the  Submaxillary  Gland  in  the  Cervical 

Sympathetic  of  the  Cat.     Amer.  Journ.  of  Physiol.,  1907,  xix.  408-416. 
W.  T.   PORTER,   H.    K.    MARKS,  and  J.    B.  SWIFT.     The  Relation  of  Afferent 

Impulses  to  Fatigue  of  the  Vasomotor  Centre.     Amer.   Journ.  of  Physioi., 

1907-1908,  xx.  444-450. 

W.  T.  PORTER  and  H.  K.  MARKS.     The  Effects  of  Haemorrhage  upon  the  Vaso- 
motor Reflexes.     Amer.  Journ.  of  Physiol.,  1908,  xxi.  460-465. 
W  .  M.    BAYLISS.     On  Reciprocal   Innervation   in   Vasomotor  Reflexes  and  the 

Action  of  Strychnine  and  of  Chloroform  thereon.     Proc.  Roy.  Soc.,  1908,  Ixxx. 

series  B,  pp.  339-375. 
W.    M.    BAYLISS.      The   Excitation    of   Vaso-dilator    Nerve-fibres    in   Depressor 

Reflexes.     Journ.  of  Physiol.,  1908,  xxxvii.  264-277. 
"W.  T.  PORTER  and  R.   RICHARDSON.     A  Comparative  Study  of  the  Vasomotor 

Reflexes.     Amer.  Journ.  of  Physiol.,  1908-1909,  xxiii.  131-140.  • 
T.    SOLLMAN  and  J.   D.   PILCHER.     The   Reactions  of  the  Vasomotor  Centre  to 

Sciatic  Stimulation  and  to  Curare.     Amer.  Journ.   of  Physiol.,   1910,   xxvi. 

233-259. 


CHAPTER   XI 

CHEMISTRY   AND    PHYSICS    OF   RESPIRATORY    EXCHANGES 

CONTENTS. — Early  notions  of  the  importance  of  respiration  (Aristotle,  Galen, 
Leonardo  da  Vinci,  van  Helmont,  Boyle,  Hook,  Fracassati,  Lower,  Mayow).  2. 
Modern  doctrines  (Black,  Bergmann,  Priestley,  Lavoisier).  3.  Theory  of  gas 
exchanges  in  the  lungs  and  tissues  (Lagrange  and  Spallanzani,  W.  Edwards). 
4.  Extraction  of  gases  from  the  blood  (Magnus,  L.  Meyer,  Hoppe-Seyler,  Ludwig, 
Prliiger).  5.  Varying  content  of  arterial,  venous,  and  asphyxiated  blood. 
6.  State  of  the  oxygen  in  the  blood.  7.  State  of  the  carbonic  acid  in  the  blood. 
8.  Tension  of  gases  in  venous  and  arterial  blood  and  in  inspired  >and  expired  air  ; 
theory  of  pulmonary  gas  exchange  by  diffusion  and  by  secretory  processes.  9. 
Theory  of  gas  exchanges  in  the  tissues.  10.  The  respiratory  quotient  and  its 
variations.  Bibliography. 

JUST  as  the  Circulation  provides  for  the  exchange  of  fluid  materials 
between  the  blood  and  the  tissues,  so  Respiration  provides  for  the 
exchange  of  gaseous  materials  between  the  environment  and  the 
blood,  and  between  the  blood  and  the  tissues. 

We  have  already  seen  that  the  function  of  respiration  is 
common  to  all  living  beings  (see  Chap.  II.  4 ;  Chap.  III.  3).  Even 
Pasteur's  anaerobes  develop  carbonic  acid,  utilising  the  oxygen 
which  is  combined  with  the  organic  substances,  and  by  its  means 
producing  exothermic  reactions,  such,  i.e.,  as  the  liberation  of  energy 
in  the  form  of  heat.  They  thus  fulfil  the  function  of  respiration, 
albeit  in  a  different  way  from  other  living  beings,  so  that  it  cannot 
be  said  that  they  do  not  breathe.  The  vast  majority  of  living 
creatures,  however,  respire  free  oxygen :  the  simplest  organisms 
directly;  those  which  have  circulating  blood,  indirectly,  i.e. 
through  the  oxygen  of  the  blood.  Among  these  last  we  dis- 
tinguish external  respiration,  or  the  gas  exchanges  between  the 
environment  and  the  blood,  from  internal  respiration,  or  the  gas 
exchanges  between  the  blood  and  the  tissues.  By  means  of  the 
first,  the  venous  blood  in  the  lungs  and  gills  is  rendered  arterial ; 
by  the  second,  the  arterial  blood  in  the  capillaries  of  the  aortic 
system  or  greater  circulation  is  rendered  venous. 

I.  The  phenomena  of  respiration  first  received  a  scientific 
explanation  in  modern  times,  although  they  arise  in  physiological 
processes  that  have  a  first  claim  on  the  attention  of  mankind. 

VOL.  I  369  2  B 


370  PHYSIOLOGY 


CHAP. 


The  need  of  breathing  is,  as  a  fact  of  common  experience,  im- 
perative; we  begin  to  breathe  when  we  begin  to  live,  we  cease 
to  breathe  when  we  die. 

Aristotle  (354  B.C.)  remarked  that  all  mammals,  including  the 
whales  which  live  in  water,  breathe  air,  and  that  fishes,  molluscs, 
and  crustaceans  breathe  the  water  in  which  they  live.  Both  air  and 
water  serve  to  refrigerate  them,  i.e.  to  temper  the  innate  heat.  He 
notices  that  the  warmer  animals  breathe  more  intensely,  and 
explains  this  on  the  supposition  that  they  had  a  greater  need  of 
refrigeration — a  confusion  of  effect  and  cause.  Animals  in  closed 
vessels  perished,  according  to  Aristotle,  because  they  warm  their 
environment,  and  can  no  longer  cool  themselves  by  respiration. 

Herophilus  and  Erasistratus,  the  leaders  of  the  Alexandrian 
School  (300  B.C.),  had  a  more  physiological  notion  of  respiratory 
phenomena.  They  described  a  systole  and  a  diastole  of  the  lungs 
(expiratory  and  inspiratory  movements),  which  permitted  the 
pneuma  to  penetrate  into  the  arteries,  whence  it  was  conducted  to 
the  different  parts  of  the  body  in  order  to  vivify,  that  is,  to  warm 
them.  It  was,  however,  Galen  (see  Chap.  VI.  2)  who  first  grasped 
the  chemical  function  of  respiration,  since  he  assumed  that  the 
vital  spirit  was  absorbed  in  the  pulmonary  diastole,  while  the 
fuliginous  vapours  were  expelled  along  with  the  water  vapour  in 
the  pulmonary  systole. 

With  Galen,  therefore,  as  we  shall  see,  begins  the  experimental 
study  of  the  mechanics  of  respiration.  His  ideas  prevailed 
unchanged  during  the  Middle  Ages.  Servetus'  book,  Eestitutio 
Christianismi,  was  the  last  echo — stifled  in  the  flames  kindled  by 
the  Catholics  of  Vienna  and  the  Calvinists  of  Geneva. 

Leonardo  da  Vinci's  conception  of  the  respiratory  function 
(1452-1519)  was  far  superior  to  Galen's  in  accuracy  and  lucidity. 
Leonardo  was  one  of  the  most  universal  geniuses  the  human  race 
has  ever  seen,  inasmuch  as  he  combined  with  the  eminent  gifts  of 
an  artist  the  experimental  instinct  and  divining  power  of  the  man 
of  science,  in  the  most  modern  sense  of  the  word.  In  the  scientific 
aphorisms  published  after  his  death  there  is  a  brilliant  study  on 
the  nature  of  a  candle  flame,  which  is  a  complex  physical  and 
chemical  problem.  In  this  study,  among  other  admirable  observa- 
tions, he  affirms  that  "  the  flame  first  disposes  of  the  material  that 
is  to  nourish  it  (i.e.  reduces  to  the  gaseous  state  the  combustible 
matter  of  the  candle),  and  then  feeds  itself  on  the  same  .  .  . 
where  the  air  is  not  fitted  to  maintain  the  flame  (i.e.  where  the 
air  has  been  consumed  by  the  flame),  no  flame  can  live,  neither 
any  terrestrial  nor  aerial  animal  .  .  .  where  flame  cannot  live,  no 
animal  that  breathes  can  sustain  existence"  (Codice  Atlantico, 
folio  170,  fasc.  XXIII.  p.  963). 

These  words,  besides  being  an  inspired  conception  of  the  analogy 
between  the  phenomena  of  combustion  and  of  respiration,  convey 


xi  KESPIKATOKY  EXCHANGES  371 

an  experimental  fact  of  the  highest  importance,  although  Leonardo 
adduces  no  evidence. 

The  first  real  discovery  in  the  field  of  experimental  chemistry 
was  made  by  Jean  Baptiste  van  Helmont  (born  at  Brussels,  1577  ;  d. 
1644),  noblest  of  the  experimental  alchemists,  precursor  of  Priestley 
and  Lavoisier,  the  founders  of  modern  chemistry.  He  found  that 
on  burning  coal  and  in  the  fermentation  of  wine,  a  gas  which  he 
called  gas  silvestre  escaped,  which  is  incapable  of  maintaining  a 
flame,  and  produces  asphyxia  and  death  in  animals.  This  gas 
may  develop  in  the  heart  of  the  earth,  as  in  the  famous  Grotta  del 
Cane  near  Naples ;  it  bubbles  up  in  certain  mineral  waters,  as  at 
Spa,  and  can  also  be  evolved  from  the  calcareous  concrements 
formed  in  the  crab's  stomach  (the  so-called  "  crab's  eyes")  by  dis- 
solving them  in  vinegar.  In  short,  van  Helmont's  gas  silvestre  is 
nothing  else  than  the  carbonic  acid  of  modern  chemists.  Haller 
used  this  discovery  of  the  Belgian  alchemist  to  refute  the  Aristo- 
telian theory  of  respiration  which  Cesalpinus  and  Harvey  had 
sought  to  resuscitate. 

In  the  year  1670  another  distinguished  philosopher  and 
investigator,  Eobert  Boyle  (1626-1691),  the  leader  of  the  group  of 
scientific  men  who  formed  the  nucleus  of  the  Koyal  Society,  proved, 
with  the  help  of  the  pneumatic  machine  introduced  by  the 
Magdeburg  physicist,  von  Guericke,  that  not  only  do  all  land 
animals  perish  in  a  vacuum,  but  all  water  animals  as  well,  showing 
that  these  equally  require  the  air  which  is  dissolved  in  the  water 
they  inhabit.  He  concluded  from  many  experiments  that  the  air 
contains  a  vital  substance — thus  adumbrating  the  oxygen  of 
modern  chemistry,  which  enters  into  the  phenomena  of  combustion, 
respiration,  and  fermentation.  He  also  confirmed,  experimentally, 
the  fact  already  advanced  by  Leonardo  da  Vinci  and  van  Helmont, 
to  the  effect  that  the  air  becomes  unbreathable  through  respiration 
— not  because  it  gets  heated,  but  because  it  suffers  chemical 
change. 

Eobert  Hook,  friend  and  contemporary  of  Boyle,  pointed  out 
the  need  of  incessant  renewal  of  the  air  in  the  lungs  for  the 
maintenance  of  life.  Vesalius  had  noticed,  a  hundred  years 
previously,  that  in  order  to  prolong  the  life  of  a  dog  after  opening 
of  the  thorax  and  consequent  retractation  of  the  lungs,  it  was  only 
necessary  to  inflate  them  rhythmically  with  air ;  but  he  brought 
forward  no  conclusions  of  importance  in  regard  to  the  physiology 
of  respiration.  Hook  perfected  the  method  of  artificial  respiration 
in  the  dog  with  opened  thorax  by  rhythmically  blowing  air  from 
a  bellows  into  the  lungs,  or  by  .continuous  insufflation  after 
making  an  opening  on  the  surface  of  each  lung.  In  both  cases  he 
saw  that  the  animal  could  be  kept  alive  for  a  prolonged  period, 
and  only  died  when  the  air  stagnated  in  the  lungs  from  cessation 
of  the  rhythmical  or  continuous  ventilation.  He  concluded  that 


372  PHYSIOLOGY  CHAP. 

the  significance  of  respiration  lay  in  the  renewal  of  the  pulmonary 
air  and  not  in  the  alternate  expansion  and  contraction  of  the 
lungs,  as  was  believed  by  certain  iatro-mechanicians. 

The  ancients  were  undoubtedly  aware  of  the  difference  in 
colour  between  arterial  and  venous  blood.  It  was  perhaps  owing 
to  this  difference  that  they  termed  the  pulmonary  artery  vein,  and 
the  pulmonary  veins  arteries.  It  was  also  known  to  the  older 
surgeons  that  the  clot  formed  from  the  blood  extracted  by  bleeding 
exhibits  the  scarlet  colour  of  arterial  blood  in  the  upper  layers,  and 
the  darker  colour  of  venous  blood  in  the  deeper  layers.  In  1665 
it  was  discovered  by  Fracassati,  a  famous  physician  of  Bologna, 
that  the  florid  colour  of  the  superficial  layer  of  the  clot  was  pro- 
duced by  the  action  of  the  air,  and  that  it  sufficed  to  invert  the 
clot  for  the  darker  layers,  which  had  been  in  contact  with  the 
walls  of  the  vessel  containing  it,  to  assume  the  same  hue  as  the 
arterial  blood. 

This  was  confirmed  by  Lower  (1669),  another  friend  and 
collaborator  of  Boyle,  who  at  the  same  time  discovered  a  further 
weighty  fact :  he  observed,  namely,  that  when  artificial  respiration 
was  used  with  the  opened  thorax,  the  venous  blood  became  arterial, 
not  in  the  heart,  but  in  the  lungs,  while  the  reduced  blood  of  the 
lungs  also  became  venous  if  artificial  respiration  was  interrupted. 

So  far  nothing  positive  was  known  about  the  chemical  processes 
that  take  place  in  respiration,  and  the  analogy  between  respiration 
and  combustion  was  merely  guessed  at,  not  proven. 

The  pioneer  in  the  chemistry  of  the  air  and  the  doctrines  of 
respiration,  combustion,  and  oxidation  of  metals  was  John  Mayow 
(1640-1679).  In  a  series  of  original  experiments  published  at  Oxford 
when  he  was  twenty-eight,  he  expressed  his  conviction  that  the 
air  was  not  a  simple  body  but  a  mixture  of  at  least  two  different 
gases  or  "  spirits/'  one  of  which  (termed  by  him  spiritus  nitro- 
aereus  or  igneo-aereus)  is  competent  to  support  life  by  passing  into 
the  blood  during  respiration,  and  rendering  it  florid  and  able  to 
ferment  and  develop  heat.  It  is  this  same  vital  gas  which 
combines  with  burning  bodies,  generates  acids,  and  rusts  iron. 
The  air  that  remains  after  the  consumption  of  the  spiritus  nitro- 
aereus  is  inadequate  for  life,  for  combustion,  for  the  rusting  of 
metals.  The  experiments  by  which  Mayow  was  led  to  these 
remarkable  results,  which  virtually  involved  the  discovery  of 
oxygen  and  nitrogen,  consisted  chiefly  in  the  introduction  of  small 
animals  and  lighted  candles  into  a  closed  vessel  over  water.  He 
noted  the  diminution  of  the  volume  of  air  in  consequence  of 
respiration  and  combustion,  and  the  cessation  of  life  and  of 
combustion  after  a  certain  time,  due  not  to  the  accumulation  of 
fumes,  but  to  the  consumption  of  the  igneo-aereal  particles. 
Unfortunately  this  genius,  who  antedated  the  greatest  discovery 
of  the  chemistry  of  the  air  by  a  century,  died  at  the  age  of  thirty- 


xi  RESPIKATOKY  EXCHANGES  373 

three,  a  few  years  after  the  publication  of  his  early  experiments. 
The  great  importance  of  his  unfinished  work  was  overlooked,  and 
it  hardly  had  any  influence  upon  the  progress  of  physiology. 

II.  Before  Mayow's  notions  of  the  composition  of  the  air  could 
be  regarded  as  a  definite  achievement,  it  was  necessary  to  perfect 
the  methods  of  investigating  the  chemical  study  of  gases,  more 
especially  the  art  of  manipulating  them  .like  solid  or  fluid  bodies. 
Many  workers  contributed  to  the  building  up  of  this  technique, 
in  particular  Hales  (1678-1*761),  who  was  the  promoter  of  the  so- 
called  pneumatic  chemistry,  by  inventing  the  method  of  collecting 
gases  in  an  inverted  test-tube,  suspended  in  a  vessel  of  water  or 
mercury  into  which  the  gas  was  passed  by  means  of  bent  tubes. 
By  this  method,  known  as  the  eudiometric,  Joseph  Black,  Professor 
at  Glasgow  in  1757,  again  isolated  and  studied  the  properties  of 
that  gas  which  van  Helmont  termed  gas  silvestre,  to  which  Black 
gave  the  name  of  "  fixed  air."  He  snowed  experimentally  that  it 
was  a  product  of  the  respiration  of  man  and  other  animals.  On 
blowing  through  lime  water  or  a  solution  of  caustic  alkali,  he  saw 
that  the  lime  was  precipitated  and  the  alkali  was  rendered  mild. 
Bergmann  of  Stockholm  subsequently  (1772)  continued  Black's 
investigations  on  "  fixed  air,"  which  he  termed  "  ae'real  acid," 
finding  it,  though  in  small  quantities,  in  the  atmosphere.  Black 
and  Bergmann,  in  these  weighty  experiments,  were  the  immediate 
precursors  of  Priestley  and  Lavoisier,  who  are  usually  accredited 
with  the  prestige  of  being  the  founders  of  modern  chemistry. 

Priestley  (1733-1804)  eagerly  pursued  the  researches  of  his 
predecessors ;  in  1772  he  experimented  with  the  object  of  seeing 
whether  it  were  possible  to  restore  the  vital  properties  of  air  that 
had  deteriorated  in  consequence  of  animal  respiration  and  com- 
bustion, and  after  many  fruitless  experiments  he  discovered  that 
plants  thrive  in  this  air  and  renew  it  for  purposes  of  animal  life 
and  combustion.  In  1775  he  discovered  that  red  precipitate  of 
mercury  on  calcination  developed  a  gas  which  was  exceedingly 
favourable  for  combustion  and  animal  respiration  ;  this  (in  accord- 
ance with  Stahl's  doctrine  which  then  predominated)  he  termed 
dephlogisticated  air,  i.e.  air  free  from  the  imaginary  principle 
known  as  phlogiston.  This  was  the  same  gas  that  Mayow  called 
nitro- ae'real  or  igneo- ae'real,  and  which  Priestley  succeeded  in 
obtaining  pure,  and  isolated  from  the  other  atmospheric  gases. 
By  various  other  processes  he  also  isolated  the  irrespirable  gas 
obtained  from  air,  after  burning  coal  or  sulphur,  and  dissolving 
the  products  of  combustion  in  water.  He  studied  the  properties 
of  this  and  called  it  phlogistic  air,  i.-e.  air  charged  with  phlogiston. 
Lastly,  in  continuation  of  the  experiments  above  described,  of 
Fracassati  and  Lower  (the  results  of  which  had  been  confirmed 
by  Cigna  and  Hewson  in  1773),  Priestley  showed  that  the  de- 
phlogisticated air  which  he  had  discovered  was  essential  for  the 


374  PHYSIOLOGY  CHAP. 

conversion  of  venous  into  arterial  blood,  and  that  the  blood,  even 
through  an  animal  membrane,  makes  normal  air  irrespirable  and 
unable  to  support  combustion,  by  converting  it  into  phlogistic  air. 

After  Priestley's  discoveries  it  remained  for  Lavoisier  (born  in 
Paris,  1743 ;  infamously  guillotined  March  8,  1794)  to  earn  the 
glory  of  rearing  a  solid  and  complete  edifice  on  their  basis,  both  as 
regards  the  chemical  composition  of  the  air,  and  the  phenomena 
of  combustion  and  respiration. 

In  order  to  refute  the  cumbrous  doctrine  of  Stahl's  phlogiston, 
it  was  only  necessary  for  Lavoisier  to  employ  the  balance,  and  to 
show  that  the  so-called  earths  or  metallic  oxides  are  heavier  than 
metals.  Stahl's  theory  presupposed  that  rnetals,  when  converted 
into  oxides,  lost  their  phlogiston,  and  therefore  lost  in  weight,  the 
oxides  on  conversion  into  metals  becoming  phlogistic  and  therefore 
gaining  in  weight.  Lavoisier  (1776)  established  that  the  air  is 
not  a  simple  fluid  which  robs  the  igneous  principle  from  animals 
and  gives  it  up  to  plants,  but  a  mixture  of  two  fluids,  one 
inadequate  to  support  life,  which  he  termed  azote,  the  other 
eminently  respirable,  which  he  called  oxygen.  The  former  corre- 
sponds with  Priestley's  phlogistic,  the  latter  with  his  dephlogis- 
ticated  air. 

In  1780  Lavoisier  discovered  the  chemical  composition  of  van 
Helmont's  gas  silvestre  (the  "  fixed  air  "  of  Black)  and  showed  it 
to  be  the  result  of  the  combination  of  carbon  with  oxygen  in 
definite  proportions.  He  succeeded  in  correlating  the  formation 
of  carbonic  acid  gas  in  expired  air  with  the  synchronous  con- 
sumption of  oxygen,  and  conceived  of  pulmonary  respiration  as  a 
phenomenon  of  combustion,  in  which,  under  the  influence  of  life, 
the  oxygen  combines  with  the  carbon  exhaled  from  the  body,  and 
becomes  the  principal  source  of  the  internal  heat  generated  by  the 
animal.  Nor  was  this  all ;  by  means  of  the  balance  he  showed 
that  the  amount  of  oxygen  consumed  in  the  respiratory  work  of 
animals  is  greater  than  that  contained  in  the  carbonic  acid  given 
off.  The  recent  discovery  of  the  chemical  composition  of  water, 
made  by  Cavendish  (1781),  and  soon  after  confirmed  by  Lavoisier, 
'enabled  him  to  account  for  this  fact  and  to  complete  his  theory  of 
the  chemistry  of  respiration,  which  he  conceived  as  a  double 
combustion,  from  which  are  formed  carbonic  acid  and  water.  He 
made  this  deduction  from  repeated  experiments,  which  enabled 
him  to  conclude  that  "respiration  is  a  slow  combustion  of  carbon 
and  hydrogen,  perfectly  similar  to  that  which  occurs  in  a  burning 
lamp  ;  and  from  this  point  of  view  animals  which  breathe  are  true 
combustible  bodies  that  burn  and  are  consumed." 

In  1789  Lavoisier  published  with  Seguin  a  large  number  of 
researches  that  are  of  fundamental  importance  to  the  theory  of 
respiration.  The  two  experimenters  noted  that  the  intensity  of 
respiratory  combustion  does  not  vary  essentially,  whether  the 


xi  EESPIEATOKY  EXCHANGES  375 

animal  breathes  pure  oxygen  or  a  mixture  of  fifteen  parts  nitrogen 
and  one  of  oxygen  ;  that  during  respiration  the  nitrogen  does  not 
sensibly  increase  nor  diminish,  and  may  without  injury  be 
substituted  for  hydrogen,  which  also  behaves  as  an  indifferent  gas  ; 
that  during  digestion  and  the  muscular  movements  the  intensity 
of  respiratory  combustion  increases ;  that  lastly,  the  consumption 
of  oxygen  in  man  increases  sensibly  when  the  external  temperature 
is  lowered. 

As  regards  the  seat  of  respiratory  combustion,  Lavoisier  was 
less  happy  than  in  his  previous  researches,  for  he  asserted  with 
Seguin  that  it  took  place  in  the  lungs,  where  the  oxygen  of  the 
air  encountered  the  combustible  material,  represented  by  a  hydro- 
carbonous  fluid.  This  hypothesis,  which  makes  the  lungs  the  seat 
of  respiratory  combustion,  was  open  to  grave  objections.  It  was 
observed  that  the  temperature  of  the  lungs  is  no  higher  than  that 
of  the  other  internal  organs,  making  it  dubious  whether  heat  could 
spread  thence  to  the  rest  of  the  body.  Starting  from  this  fact, 
Lagrange  (born  at  Turin,  1736  ;  died  1813),  one  of  the  most 
illustrious  of  mathematicians,  was  the  first  to  rectify  Lavoisier's 
error.  He  maintained  the  hypothesis  that  only  gas  exchanges 
take  place  in  the  lungs,  in  which  the  blood  circulating  through 
them  yields  its  carbonic  acid  to  the  air  and  absorbs  oxygen  from 
it ;  and  that  respiratory  combustion  is  accomplished  in  every  part 
of  the  body  to  which  the  blood  circulates. 

III.  The  earliest  experimental  proofs  of  the  theory  of  internal 
or  tissue  respiration,  as  foreshadowed  by  Lagrange,  were  given  by 
Lazzaro  Spallanzani  (1729-1799),  who  claims  an  important  place 
in  the  history  of  the  chemistry  of  respiration.  In  a  long  series  of 
comparative  studies  on  the  respiration  of  a  great  number  of 
animals,  terrestrial,  aquatic,  vertebrate,  aud  invertebrate,  he 
extended  the  doctrine  of  Lavoisier,  proving  that  oxygen  is  in  every 
case  essential  to  life,  and  that  in  all  it  is  absorbed  by  the  organs  of 
respiration  (lungs,  gills,  trachea,  skin)  and  carried  to  the  circula- 
tion, where  it  determines  the  vitality  of  the  tissues  by  entering 
into  combination  with  them. 

Further,  by  ingenious  experiments  on  snails  he  showed  that 
excretion  of  carbonic  acid  is  independent  of  absorption  of  oxygen, 
since  it  remains  almost  always  constant,  even  when  these  creatures 
are  enclosed  in  tubes,  plunged  in  a  mercury  bath,  and  filled  either 
with  water  that  has  been  boiled  and  deprived  of  gases  by  the  air- 
pump,  or  with  nitrogen  or  hydrogen. 

The  Memorie  su  la  respirazione  is  the  posthumous  work  of  the 
Abbe*  Spallanzani,  and  contains  only  a  few  of  his  observations. 
After  his  death  the  protocols  of  his  experiments  were  confided  to 
his  friend  the  Genevese  scientist  and  librarian,  Jean  Senebier,  who 
extracted  from  them  the  materials  for  a  work  entitled  Rapport  de 
I'air  avec  les  dtres  organises  (Geneva,  1807).  This  is  a  valuable 


376  PHYSIOLOGY  CHAP. 

collection  of  experimental  facts,  showing  how  much  of  the  progress 
of  our  science  is  due  to  this  illustrious  physiologist.  Undeniably, 
however,  it  lacks  that  concise  method  and  critical  elaboration 
which  it  would  have  received  had  the  author  been  able  to  complete 
his  own  work. 

The  subsequent  researches  of  William  Edwards  (born  in 
Jamaica,  1*776;  died  Versailles,  1842)  were  on  the  lines  of 
Spallanzani's  most  important  experiments.  On  bringing  frogs, 
whose  luugs  had  been  emptied  by  compression  of  the  flanks,  under 
a  bell-jar  of  hydrogen  immersed  in  mercury,  Edwards  observed 
that  the  animal  in  the  space  of  a  few  hours  developed  an  amount 
of  carbonic  acid  almost  equal  to  the  volume  of  its  body.  Similar 
results  were  obtained  from  experiments  on  fish,  which  breathe 
through  their  gills.  In  order  to  prove  that  the  same  fact  holds 
for  mammals,  which  die  as  soon  as  they  are  deprived  of  oxygen,  he 
took  newborn  animals,  which  have  a  longer  resistance  to  asphyxia, 
and  showed  that  when  immersed  in  an  atmosphere  of  hydrogen, 
they  continue  to  exhale  carbonic  acid.  These  facts  are  only  the 
confirmation  and  generalisation  of  those  enunciated  twenty-five 
years  earlier  by  Spallanzani ;  but  Edwards  deduced  from  them 
more  clearly  and  explicitly  the  erroneous  nature  of  Lavoisier's 
theory  of  pulmonary  combustion,  and  the  proof  of  Lagrange's 
theory  of  pulmonary  gas  exchanges.  Carbonic  acid  (as  he 
approximately  concluded)  is  exhaled  from  the  body  independent  of 
the  entrance  of  oxygen  into  the  lungs  and  its  absorption  by  the 
blood.  It  is  probably  derived  from  the  tissues,  and  may  be 
already  formed  and  dissolved  in  the  venous  blood,  from  which  it  is 
exhaled  on  circulating  through  the  pulmonary  vessels. 

Collard  de  Martigny  (1830),  Johannes  Miiller  (1835),  Bischoff 
(1837),  Marchand  (1844),  with  improved  and  varied  methods  of 
experiment,  obtained  the  same  results  as  Spallanzani  and 
Edwards. 

IV.  The  theory  of  external  respiration  as  a  gaseous  exchange 
between  the  air  contained  in  the  pulmonary  alveoli  and  the  blood 
gases  circulating  in  the  pulmonary  capillaries,  and  the  theory  of 
internal  respiration  in  the  sense  of  a  gaseous  exchange  between 
the  blood  gases  circulating  in  the  aortic  capillaries  and  those 
produced  by  the  living  elements  of  all  the  tissues,  received  a  solid 
experimental  basis  from  the  researches  on  the  quality  and  quantity 
of  the  gases  contained  in  the  blood,  and  the  inter-comparison  of 
the  gases  extracted  from  arterial  and  those  extracted  from  venous 
or.asphyxial  blood. 

When  in  1824  Edwards  published  his  essay,  The  Influence  of 
Physical  Agents  on  Life,  in  which  the  theory  of  the  respiratory 
gas  exchanges  was  clearly  formulated,  some  scanty  data  existed  in 
support  of  the  hypothesis  that  the  blood  was  the  vehicle  of  these 
exchanges,  and  held  in  solution  or  loose  combination  both  the 


xi  EESPIKATORY  EXCHANGES  377 

oxygen  and  the  carbonic  acid.  The  blood  gases  were  first  extracted 
with  the  vacuum  pump  by  Boyle  and  Mayow ;  Humphry  Davy 
(1803)  was  the  first  to  extract  them  by  the  method  of  warming, 
and  to  recognise  that  arterial  blood  contains  little  carbonic  acid 
and  much  oxygen. 

Priestley  (1776),  Fontana  (1804),  Nasse  (1816),  Brande  (1818), 
Vauquelin  (1820)  and  others  were  able  either  by  the  method  of 
simple  diffusion,  by  bringing  the  blood  into  contact  with  indifferent 
gases  such  as  hydrogen  and  nitrogen,  or  by  agitating  the  blood  with 
the  said  gases  or  passing  them  through  it,  to  determine  the  fact  that 
it  holds  both  oxygen  and  carbonic  acid  in  solution.  These  results, 
obtained  with  somewhat  loose  methods,  were,  however,  contested 
by  other  distinguished  physiologists,  so  that  John  Davy,  Johannes 
Miiller,  Gmelin,  Tiedemann  and  others  agreed  in  denying  the 
presence  of  free  gases  in  the  blood,  while  Vogel,  Nasse,  Scudamore, 
Th.  Bischof,  Collard  de  Martigny,  and  van  Enschut  maintained 
that  carbonic  acid  was  not  found  in  the  blood  in  a  state  of 
solution. 

It  was  Magnus  (1837),  Professor  of  Physics  at  Berlin,  who  put 
an  end  to  this  uncertainty,  and  performed  his  experiments  on  the 
gases  of  the  blood  with  the  scientific  method  that  was  indispensal  >le 
to  make  his  results  convincing.  He  extracted  the  gases  of  the 
blood  by  means  of  the  Torricellian  vacuum,  with  an  ingenious 
apparatus  which  as  it  were  combined  the  mercury  pump  and  the 
pneumatic  machine.  As  the  result  of  his  analysis,  he  stated  that 
both  arterial  and  venous  blood  contain  not  only  carbonic  acid,  but 
oxygen  and  nitrogen  as  well,  and  that  carbonic  acid  preponderates 
in  venous,  oxygen  in  arterial  blood.  He  was  the  first  who  attempted 
to  account  for  the  mechanism  of  the  pulmonary  gas  exchanges, 
considered  as  an  effect  of  simple  diffusion,  according  to  the  physical 
law  formulated  by  J.  Dalton  in  1805. 

In  1857,  however,  Lothar  Meyer  demonstrated  that  the  amount 
of  oxygen  liberated  from  the  blood  does  not  increase  proportionally 
with  the  lowering  of  pressure,  as  it  should  according  to  Dalton's 
law,  and  that  it  is  only  when  the  pressure  acting  on  the  blood  is . 
reduced  to  -fa  that  the  oxygen  of  the  blood  begins  to  dissociate. 
On  combining  the  vacuum  method  of  extracting  the  blood  gases 
with  the  method  of  heating  to  40°  C.  blood  that  had  been 
extracted  and  diluted  with  a  quantity  of  water  previously  boiled 
and  deprived  of  its  gases,  he  completed  and  partially  rectified  the 
conclusions  of  Magnus. 

While  approximately  true,  Meyer's  data  were  not  yet  entirely 
accurate,  as  was  shown  by  the  succeeding  work  of  Hoppe-Seyler 
(1854),  Ludwig  (1858),  and  Pfliiger  (1865).  They  introduced  in- 
teresting improvements  in  technique,  with  the  object  of  obtaining 
the  maximal  quantity  of  gases  that  can  be  extracted  from  a  given 
quantity  of  arterial,  venous,  or  asphyxial  blood.  In  order,  as 


378  PHYSIOLOGY  CHAP. 

briefly  as  possible,  to  condense  the  more  important  conclusions 
arrived  at  in  the  actual  state  of  science,  we  must  pass  from  the 
historical  exposition  of  the  subject  to  a  summary  of  the  experimental 
data. 

Laws  of  Absorption  and  Diffusion  of  Blood.  —  In  order  to  'understand 
what  follows  in  regard  to  the  mechanism  of  respiratory  gas  exchanges,  it  is 
necessary  to  recapitulate  certain  physical  laws  which  are  closely  bound  up 
with  this  process. 

Since  gases  have  no  definite  shape  like  solids,  nor  definite  volume  like 
liquids,  and  since  the  molecules  which  constitute  them  have  the  property  of 
mutual  repulsion,  so,  when  two  gases  that  do  not  enter  into  chemical  com- 
bination, are  brought  into  contact,  they  promptly  expand  one  into  the  other, 
until  they  form  a  uniform  mixture  independent  of  their  different  densities. 
This  phenomenon  is  called  the  diffusion  of  gaseV 

The  force  with  which  the  molecules  of  the  gases  tend  to  expand  in  a  space, 
and  by  means  of  which  they  exert  uniform  pressure  in  every  direction,  is 
called,  the  tension  of  gases.  Obviously,  the  greater  the  number  of  gaseous 
molecules  brought  together  in  a  confined  space,  the  greater  will  be  the  pressure. 
It  follows  that  the  tension  of  a  gas  is  inversely  proportional  to  its  volume 
(Mariotte's  law). 

Again,  when  two  gases  are  separated  by  a  porous  septum,  there  is  reciprocal 
diffusion,  but  the  velocity  with  which  the  molecules  of  each  diffuse  across  the 
septum  varies  according  to  their  densities  ;  the  lighter  gases,  such  as  H  and 
CH4,  diffuse  more  rapidly  than  Cl  and  CO,  which  are  heavier.  It  may  be 
said  approximately,  with  Graham,  that  the  rate  at  which  gases  traverse  the 
pores  of  the  septum  is  inversely  proportional  to  the  square  root  of  their 
densities. 

There  is  a  marked  attraction  between  gases  and  particles  of  solid  porous 
bodies,  whereby  the  former  are  attracted  and  condensed  between  the  pores  of 
the  latter.  Thus,  for  example,  1  vol.  of  boxwood  charcoal  may  condense  at 
12°  C.,  and  at  ordinary  barometric  pressure,  35  vols.  of  C02,  9'4  vols.  of  O2,  7'4 
vols.  N,  1-75  vols.  H2.  This  process  is  termed  the  absorption  of  gases  by  solid 
bodies,  and  is  •  invariably  accompanied  by  evolution  of  heat  in  ratio  with  the 
energy  with  which  the  absorption  proceeds.  Non-porous  bodies,  too,  are 
capable  of  condensing,  if  not  of  absorbing  on  their  surface,  a  layer  of  the  gases 
with  which  they  may  be  brought  into  contact. 

More  important  for  us  is  the  absorption  of  gases  by  liquids.  In  this  con- 
nection it  has  been  found  that  the  volume  of  a  gas  absorbed  by  a  liquid  is 
independent  of  its  pressure.  Since,  however,  the  density  of  a  gas  is  pro- 
portional to  the  pressure  under  which  it  is  placed,  and  since  its  weight  is 
equal  to  the  product  of  volume  x  density  (Boyle,  1662 ;  Mariotte,  1679),  it 
follows  that  the  weight  of  gas  absorbed  by  a  liquid  is  proportional  to  the 
pressure,  although  its  volume  remains  the  same  (Dalton-Henry  law).  Hence 
the  gas  must  be  regarded  as  physically  absorbed  by  the  liquid,  whence  it  can 
be  recovered  in  quantities  proportional  by  weight  to  the  lowering  of  pressure 
to  which  it  is  subjected.  When,  therefore,  the  pressure  is  reduced  to  zero  by 
the  Torricellian  vacuum,  the  liquid  can  be  deprived  of  all  the  gases  which  it 
has  absorbed.; 

The  absorption  coefficient  of  a  liquid  for  a  gas  is  the  figure  which  indicates 
that  volume  of  gas  which  at  0°  C.  and  760  mm.  Hg  pressure,  is  absorbed  by 
the  unit  volume  of  the  liquid  (Bunsen). 

Temperature  has  great  influence  on  coefficients  of  absorption.  A  liquid 
absorbs  less  gas,  in  proportion  as  its  temperature  is  higher,  and  at  boiling- 
point  there  is  no  longer  any  absorption.  It  is  therefore  sufficient,  in  order  to 
extract  the  gases  absorbed  by  any  liquid,  to  heat  it  to  boiling-point. 

The  degree  in  which  different  liquids  absorb  the  same  gas,  and  in  which 


XI 


EESPIEATOKY  EXCHANGES 


379 


the  different  gases  are  absorbed  by  the  same  liquid,  varies  considerably. 
volume  of  distilled  water  is  capable  of  absorbing  : — 


One 


c. 

N. 

02. 

C02. 

Air. 

0 

0-020 

0-041 

1797 

0-025 

5 

0-018                   0-036 

1-500 

0-022 

15 

0-015                   0-030 

1-002 

O'OIS 

37 

0-012                   0-025 

0-530 

0-015 

Indifferent  salts  which  are  .incapable  of  combining  chemically  with  gases, 
lower  the  absorption  coefficients  in  watery  solutions  in  proportion  to  their 
concentrations. 

In  the  body  it  is  always  with  gaseous  mixtures  in  the  fluids  of  the  tissues, 
and  never  with  isolated  gases,  that  we  have  to  deal.  We  must,  thereforer 
investigate  the  absorption  of  gas  mixtures  by  liquids.  Since  gases  exert  no 
reciprocal  pressure,  one  volume  of  liquid  may  absorb  several  gases  successively 
or  simultaneously,  in  different  volumes,  according  to  the  respective  co- 
efficients of  absorption,  and  each  gas  absorbed  is  at  a  tension  proportional 
with  the  volume  that  it  occupies  in  the  mixture  of  absorbed  gases.  Bunsen 
gave  to  this  the  name  of  partial  pressure,  because  it  represents  the  pressure 
(in  mm.  Hg)  which  each  gas  would  exert  in  the  surrounding  atmosphere,  if 
there  were  neither  absorption  nor  emission  of  gas  on  the  part  of  the  liquid. 
Since,  e.g.,  the  average  pressure  of  atmospheric  air  is  760  mm.  Hg,  and  it 
consists  in  round  numbers  of  21  vols.  per  cent  O2  and  79  vols.  per  cent 
N,  the  partial  pressure  of  the  oxygen  absorption  will  be  equal  to 
0-21  x  760=160  mm.  Hg,  and  the  partial  pressure  at  which  the  absorption  of 
N  occurs  is  equal  to  0-79  x  760  =  600  mm.  Hg. 

During  absorption  each  gas  of  the  mixture  diffuses  in  the  liquid  in  an 
amount  proportional  to  the  difference  in  concentration  of  the  adjacent  layers, 
as  Graham  shows  for  other  substances  in  solution.  Diffusion  ceases  and 
absorption  is  complete  when  in  all  layers  of  the  liquid,  and  in  the  atmosphere 
with  which  it  is  in  relation,  complete  equilibrium  of  tension  for  each  of  the 
gases  contained  in  the  atmosphere,  or  dissolved  in  the  liquid,  is  established. 

The  rate  of  diffusion  of  a  gas  through  a  layer  of  liquid  stands  in  direct 
ratio  witli  the  solubility  coefficient  of  the  gas,  and  in  inverse  ratio  with  the 
square  root  of  its  density.  So  that,  e.g.,  although  the  diffusion  rate  of  the 
molecules  of  H2  is  greater  than  that  of  the  molecules  of  C02,  the  latter  being 
more  soluble  in  water  than  the  former,  more  C02  than  H2  passes  through  a 
layer  of  liquid  in  a  given  time. 

Generally  speaking,  the  velocity  of  diffusion  of  a  gas  in  a  liquid  is  very 
low  (Duncan  and  Hoppe-Seyler,  1894).  They  found  that  at  ordinary 
barometric  pressure  and  mean  temperature,  atmospheric  air  penetrates 
extremely  slowly  into  a  given  quantity  of  water  closed  on  all  sides, 
save  at  the  top  where  the  air  enters.  After  fourteen  days  of  contact, 
absorption  in  the  lower  layers  of  the  column  of  water  was  still  incomplete. 

V.  The  most  important  conclusions  from  the  work  carried  out 
under  the  directions  of  Ludwig  and  Pfliiger  confirm  the  fact 
already  determined  by  Magnus,  to  the  effect  that  the  amount  of 
gas  that  can  be  extracted  from  arterial  blood  differs  considerably 
from  that  of  venous  blood. 

From  the  average  of  twelve  analyses  performed  by  Pfliiger  with 
the  rapid  method,  it  appears  that  the  arterial  blood  of  the  dog 


380  PHYSIOLOGY  CHAP. 

contains  22'6  vols.  per  cent  of  oxygen  (at  0°  C.  and  760  mm.  Hg), 
34'3  per  cent  of  carbonic  acid,  and  1/8  per  cent  of  nitrogen. 

According  to  an  analysis  of  Setschenow,  human  arterial  blood 
contains  21-6  vols.  per  cent  oxygen,  40*3  per  cent  carbonic  acid, 
1/5  per  cent  nitrogen.  Some  analyses  of  the  blood  of  herbivores 
(sheep,  rabbit)  made  by  Sczelkow  and  Walter  give  10'7-13'2 
vols.  per  cent  oxygen,  34-45  per  cent  carbonic  acid,  1/8-2-1  per 
cent  nitrogen. 

The  gas  content  of  venous  blood  is  more  variable,  according  to 
analysis,  since  it  depends  on  the  circulatory  velocity  and  activity 
of  metabolism  in  the  several  tissues  traversed.  At  present  we 
have  only  analyses  of  the  blood  of  the  right  heart,  in  which  the 
reduced  venous  blood  from  the  whole  aortic  capillary  system  meets 
and  mingles.  On  the 'average  of  numerous  analyses  given  in  the 
tables  of  Zuntz,  the  venous  blood  of  the  dog  contains  7*15  vols. 
per  cent  oxygen  less  than  the  arterial  blood,  8 '2  vols.  per  cent 
more  carbonic  acid,  and  much  the  same  quantity  of  nitrogen,  as 
arterial  blood. 

After  asphyxia  pushed  so  far  as  to  kill  the  animal,  the  oxygen 
does  not  disappear  from  the  whole  of  the  blood,  while  the  carbonic 
acid  increases  considerably.  From  a  number  of  analyses  of 
asphyxial  blood  made  by  Setschenow,  Holmgren  and  others,  it 
appears  to  contain  0'96  vols.  per  cent  oxygen  and  49 '53  per 
cent  carbonic  acid :  i.e.  there  is  a  deficit  of  17'3  vols.  per  cent 
oxygen  and  1043  per  cent  excess  carbonic  acid,  as  compared  with 
normal  arterial  blood,  according  to  the  values  obtained  by  the  said 
authors. 

Method  of  Extracting  Gases  from  the  Blood.  —  The  various  forms  of 
apparatus  adopted,  after  Magnus,  for  the  mechanical  extraction  of  gases  from 
the  blood,  are  those  of  Hoppe-Seyler,  Ludwig,  Lothar  Meyer,  A.  Schmidt, 
Pfliiger,  etc.  They  are  all  based  essentially  upon  the  Torricellian  vacuum, 
and  aim  at  liberating  the  gases  dissolved  in  the  fluids  or  held  in  loose 
combination.  The  most  perfect  form  for  the  rapid  and  complete  extraction 
of  gases  is  that  of  Pfliiger,  as  represented  in  Fig.  167. 

It  consists  of  three  principal  parts :  the  bulb  A  which  receives  the 
'blood  direct  from  the  artery  or  vein  ;  the  tube  for  absorption  of  the  water 
vapour  to  dry  the  extracted  gases  B ;  the  mercury  pump  CD  for  aspiration 
and  the  reverse,  i.e.  production  of  the  Torricellian  vacuum,  and  expulsion  of 
the  gases  extracted  into  the  eudiometer  tube  for  analysis. 

The  details  of  construction  of  the  apparatus  are  so  plain  on  the  diagram 
that  a  minute  description  is  superfluous. 

The  bulb  G  is  first  connected  with  the  tube  H  by  turning  the  3-way  tap 
G.  The  vessel  D  is  then  raised  by  the  handle  £,  so  that  the  whole  of  bulb 
(7,  with  which  D  communicates  by  means  of  the  strong  rubber  band  Fand 
the  glass  tube  E,  is  filled  with  mercury.  When  G  is  full,  communication 
with  H  is  closed  by  a  quarter  turn  of  the  tap  G,  and  opened  to  the  tube 
connected  with  the  desiccating  apparatus  £,  and  also  with  the  double  bulb  A, 
after  opening  the  tap  P.  The  vacuum  is  then  started  in  the  apparatus  by 
lowering  the  vessel  D  by  means  of  the  handle  £,  on  which  all  the  mercury 
passes  from  G  into  D,  and  air  rushes  in  from  A  and  B  to  G.  The  tap 


XI 


BESPIKATOKY  EXCHANGES 


381 


G  is  then  brought  back  to  its  first  position  by  a  quarter  turn,  so  that  C  is  now 
connected  with  H  and  no  longer  with  A  and  5,  while  the  vessel  I)  is  once 
more  raised,  driving  the  air  out  of  (7,  which  fills  with  mercury.  Frequent 
repetition  of  this  process  (of  turning  the  tap  G,  alternately  with  raising  and 
lowering  of  the  vessel  D  of  the  mercury  pump)  produces  a  perfect  vacuum 
throughout  the  apparatus,  which  occurs  at  the  exact  moment  at  which  the 


FIG.  167. — Pfliiger's  apparatus  for  extraction  of  blood  gases.    (Explanation  in  text.) 


mercury  of  the  manometer  0,  attached  to  the  tube  that  connects  C  with  #, 
falls  to  zero.  The  steadiness  or  oscillations  of  the  manometer  column  show 
whether  the  apparatus  is  air-tight  or  not. . 

After  making  a  perfect  vacuum,  the  pointed  upper  end  of  the  bulb  A  is 
connected  with  the  cannula  previously  introduced  into  the  blood-vessel 
(carotid  or  jugular).  The  2-way  tap  M  is  turned  so  as  to  fill  the  connecting 
tube  with  blood  which  drives  the  air  out,  after  which  another  quarter  turn 
of  the  same  tap  lets  the  blood  flow  in  the  required  quantity  into  the  bulb  A. 


382  PHYSIOLOGY  CHAP. 

Directly  the  blood  rushes  into  the  vacuum  it  froths  up,  owing  to  I  the 
liberation  of  the  gases.  The  froth  collects  in  the  upper  part  of  the  bulb,  and 
cannot  pass  through  the  minute  aperture  of  the  cock  P.  In  order  to 
promote  and  complete  the  extraction  of  the  gases,  a  cylinder  of  water  heated  f 
to  about  60°  C.  may  be  applied  to  the  exterior  of  A.  The  gases  liberated 
from  the  blood  pass  into  the  absorption  tube  B  (which  contains  con- 
centrated sulphuric  acid  in  its  lower  end,  and  bits  of  dried  pumice-stone 
saturated  with  the  same  acid  along  its  length)  and  lose  their  water  vapour, 
so  that  only  dried  gases  reach  the  vessel  G  and  are  ready  for  chemical 
analysis. 

The  amount  of  blood  run  into  the  apparatus  is  next  determined.  Since 
the  total  capacity  of  the  receiver  is  known,  the  amount  of  water  still 
required  to  fill  it  at  the  end  of  the  experiment  is  subtracted — the  difference 
representing  the  volume  of  the  blood  employed.  The  determination  is  more 
exact  if  the  amount  of  water  absorbed  in  the  tube  B  is  calculated  by  weighing 
B  before  and  after  the  experiment. 

For  quantitative  determination  of  the  gases  extracted  from  the  given 
amount  of  blood,  they  must  be  allowed  to  pass  from  the  holder  C  into  the 
eudiometer  tube  K,  which  is  filled  with  mercury  and  inverted  over  the 
mercury  trough  /.  This  is  easily  done  by  making  connection  between  C 
and  K  by  the  tap  G  through  H,  closing  the  connection  between  C  and  B,  and 
raising  the  vessel  D  by  the  handle  L,  so  that  G  acts  as  a  pressure -pump. 
Frequent  repetition  of  this  process  drives  all  the  extracted  gases  into  the 
eudiometer. 

To  determine  the  volume  of  the  C02,  a  pellet  of  caustic  potash,  moistened 
at  the  surface  arid  fused  at  the  end  to  a  platinum  wire,  is  introduced  into  the 
eudiometer.  When  all  the  carbonic  acid  is  converted  into  potassium 
carbonate,  the  pellet  is  removed  by  cautiously  withdrawing  the  platinum 
wire.  The  diminution  in  volume  of  the  gas  in  the  eudiometer  gives  the 
volume  of  C02  extracted  from  the  blood. 

The  volumetric  determination  of  the  02  is  effected  in  a  similar  way 
by  introducing  a  pellet  of  phosphorus  on  a  platinum  wire,  or  a  ball  of  filter- 
paper  saturated  with  a  solution  of  pyrogaUic  acid  in  caustic  potash,  which 
greedily  absorbs  oxygen.  After  the  ball  has  been  removed,  the  further 
diminution  of  gas  in  the  eudiometer  shows  the  volume  of  02  extracted  from 
the  blood. 

The  volume  of  gas  remaining  in  the  eudiometer  after  the  absorption  of 
C02  and  O2  consists  of  nitrogen. 

VI.  Some  notion  of  the  quantity  of  the  gases  that  can  be 
extracted  from  the  blood  is  a  necessary  premiss  to  determining 
the  state  in  which  they  are  found,  whether  free,  or  in  simpb 
physical  solution,  or  in  chemical  combination. 

As  regards  oxygen,  it  may  be  argued  from  the  large  amount 
contained  in  the  blood  that  it  cannot  be  merely  in  a  state  of\ 
solution.      As  a  matter  of  fact  the  coefficient  of  absorption  of' 
water  for  oxygen  stands  at   a   rather  low  figure ;   at  0°  C.  and  \ 
760  mm.  Hg,  of  an  atmosphere  of  pure  oxygen,  not  more  than 
4  vols.  per  cent  are  absorbed,  hence  from  the  air  (in  which  the 
partial  pressure  of  oxygen   is   five  times  less)  under  1  vol.  per 
cent  is  absorbed.     On  raising  the  temperature  of  the  water  to  that 
of  the  body,  the  coefficient  of  absorption  for  oxygen  is  still  further 
lowered.     It  is  also  lowered  considerably  if  the  water  is  replaced 
by   a   watery  solution   isotonic  with   blood  plasma.      Obviously,  / 


xi  RESPIKATOEY  EXCHANGES  383 

therefore,  the  22  -  vols.  of  oxygen  contained  in  arterial  blood 
must,  to  a  large  extent,  be  in  a  state  of  chemical  combination 
(Liebig,  1851 ;  L.  Meyer  and  Fernet,  1857).  We  know,  in  fact,  that 
the  oxygen  absorbed  by  the  blood  is  in  loose  combination  with  the 
haemoglobin  of  the  erythrocytes,  which  gives  rise  to  the  formation 
of  oxy haemoglobin  (Hoppe-Seyler,  1864 ;  see  Chap.  IV.  7). 

The  proof  of  this  fact,  one  of  capital  importance  in  the 
physiology  of  the  respiratory  exchanges,  is  that  a  watery  solution 
of.  14  per  cent  pure  haemoglobin  (which  corresponds  to  the  normal 
haemoglobin  content  of  the  blood)  is  capable  of  absorbing  and 
chemically  fixing  as  much  oxygen  as  an  equal  volume  of  blood,  and 


FIG.  168. — Curve  to  show  percentage  variations  of  oxy  haemoglobin  in  a  solution  of  14  per  cent  blood - 

Sigment,  with  variations  of  partial  pressure  of  the  atmospheric  oxygen  with  which  it  comes 
i  contact.    (Hiifner.)     Quantity  of  oxyhaemoglobin  in  Tfn  along  axis  of  ordinates  ;  partial 
pressure  of  oxygen  in  mm.  Hg,  along  axis  of  abscissa. 

by  means  of  the  Torricellian  vacuum  it  is  possible  to  extract  as 
much  oxygen  from  the  same  solution  as  from  blood. 

It  was  fundamental  to  the  conception  of  oxygen  absorption  in 
the  blood,  to  determine  to  what  point  the  quantity  that  combines 
with  haemoglobin  depends  on  its  partial  pressure  in  the  atmosphere. 
Bohr  (1885)  and  Hiifner  (1888)  made  a  number  of  experiments 
with  this  object.  The  method  consisted  in  placing  a  given  quantity 
of  defibrinated  blood,  or  better,  of  14  per  cent  solution  of  pure  haemo- 
globin (which,  as  we  have  said,  corresponds  with  the  haemoglobin 
content  of  the  blood)  in  contact  either  with  normal  air,  or  with 
artificial  air  containing  a  considerably  less  amount  of  oxygen  per 
cent;  and  then  shaking  it.  It  is  then  determined  how  much 
oxygen  combines  with,  or  is  dissociated  from,  the  haemoglobin 
on  a  rise  or  fall  of  its  partial  pressure  in  the  mixture  of  gases 
Hufner's  results  are  clearly  expressed  in  the  diagram  (Fig.  168), 


384  PHYSIOLOGY  CHAP. 

which  represents  the  curve  of  dissociation  of  oxygen  and  haemo- 
globin, in  proportion  with  the  fall  of  partial  pressure  in  the  mixture 
of  gases.  The  curve  shows  that  at  the  partial  pressure  of  150  mm. 
Hg  (which  is  a  little  lower  than  that  of  the  oxygen  of  normal  air) ' 
almost  the  whole  of  the  haemoglobin  (about  98  per  cent)  combines 
with  the  oxygen  ;  that  the  dissociation  proceeds  very  slowly  till  a 
partial  pressure  of  50  mm.  (which  corresponds  to  about  a  third  of 
the  partial  pressure  of  the  oxygen  of  normal  air)  is  reached ;  and 
that  it  only  becomes  rapid  at  a  partial  pressure  of  25  -  10  -  5  mm.  Hg, 
These  results  show  that  the  blood,  in  consequence  of  the  chemical 
affinity  of  haemoglobin  for  oxygen,  is  able  to  provide  itself  with  an 
abundant  supply,  even  when  the  organism  is  breathing  an  atmo- 
sphere very  poor  in  this  gas  ;  while,  on  the  other  hand,  the  absorption 
of  oxygen  in  the  blood  cannot  rise  far  above  the  normal,  even  when 
the  organism  is  made  to  respire  an  atmosphere  of  pure  oxygen. 

A  proof  of  this  great  independence  of  the  absorption  of  the 
oxygen  of  the  blood  from  its  partial  pressure  in  the  atmosphere  is 
shown  in  the  fact  that  mammals  do  not  exhibit  any  visible  dis- 
turbance of  respiratory  function  when  they  are  made  to  'breathe  an 
artificial  atmosphere  three  times  richer,  or  one-half  poorer  in  oxygen 
than  the  normal  air ;  and  it  is  only  when  the  partial  pressure  of 
oxygen  falls  below  this  limit  that  the  respiratory  movements  are 
progressively  accelerated,  and  death  from  lack  of  oxygen  only 
occurs  when  the  partial  pressure  of  00  is  lowered  to  3*5  mm.  Hg 
(W.  Mliller,  P.  Bert). 

On  examining  in  dogs  how  the  oxygen  content  of  arterial  blood 
varies  with  the  progressive  rarefaction  of  the  atmospheric  air 
respired,  it  was  found  that  it  remains  normal  up  to  a  total 
pressure  of  410  mm.  Hg;  that  it  diminishes  slightly  at  a 
pressure  378-365  mm.  (  =  about  half  an  atmosphere) ;  and  that  it  is 
only  at  a  total  pressure  of  300  mm.  that  any  conspicuous  diminu- 
tion of  oxygen  can  be  observed  in  arterial  blood  (Frankel  and 
Geppert).  These  facts  agree  with  the  observations  made  during 
aerostatic  ascents,  which  show  that  respiratory  disturbances  only 
begin  at  a  height  of  5000  meters  (  =  400  mm.  Hg).  On  the 
other  hand,  it  has  been  observed  on  the  high  plains  of  the  Andes 
that  men  and  animals  can  live  as  well  at  4000  metres  altitude  as  at 
the  level  of  the  sea. 

Not  quite  the  whole  of  the  oxygen  is  in  chemical  combination 
with  haemoglobin ;  a  small  fraction  of  it  (0'1-0*2  vols.  per  cent) 
is  normally  held  in  solution  in  the  plasma.  This  quantity  is, 
however,  less,  under  normal  conditions,  than  what  can  be  absorbed 
by  an  equal  volume  of  distilled  water  at  the  same  tempera- 
ture. It  may  vary  according  to  the  Henry-Dalton  law,  i.e.  the 
volume  of  oxygen  dissolved  in  the  plasma  is  proportional  to  its 
tension.  In  proportion  as  the  tissue  elements  absorb  the  oxygen 
of  the  plasma,  and  the  tension  lessens,  there  must  necessarily 


xi  EESPIKATOKY  EXCHANGES  385 

be  dissociation  of  the  haemoglobin  of  the  erythrocytes  from  the 
oxygen,  which  diffuses  in  the  plasma  to  re-establish  equilibrium 
between  the  tension  of  the  oxygen  in  the  plasma  and  the  corpuscles. 

VII.  The  carbonic  acid  of  the  blood  is  also  for  the  most  part 
in  chemical  combination,  and  to  a  minimal  extent  in  solution. 
This  is  proved  by  the  fact  that  the  coefficient  of  absorption  of  this 
gas  in  water,  at  37°  C.,  is  about  0  57,  while  on  the  other  hand  we 
have  seen  that  arterial  blood  only  contains  34  and  venous  blood  42 
vols.  per  cent.  Unlike  oxygen,  however,  which  enters  into  com- 
bination only  with  haemoglobin,  carbonic  acid  unites  chemically 
with  many  substances,  both  of  the  plasma  and  of  the  corpuscles. 

Among  the  substances  capable  of  holding  the  carbonic  acid  of 
the  blood  in  readily  dissociable  forms,  great  stress  was  formerly 
laid  upon  sodium  carbonate,  which  as  a  base  (see  p.  132)  abounds  in 
the  ash  of  plasma.  The  phenomena  of  electrolytic  dissociation  of 
the  solutions  of  this  salt  have,  however,  demonstrated  that  it  can 
only  be  of  very  secondary  importance  in  the  chemical  combination 
of  the  carbonic  acid  of  the  plasma,  by  converting  it  into  bi-carbonate. 
In  fact,  according  to  the  researches  of  Bohr,  a  very  dilute  solution 
of  015  per  cent  sodium  carbonate  becomes  almost  saturated  at  a 
pressure  of  only  10  mm.  Hg  of  carbonic  acid,  while  on  raising  the 
pressure  to  120  mm.  there  is  no  appreciable  increase  in  the  amount 
fixed  or  dissolved.  Hence  it  is  evident  that  sodium  carbonate  is 
incapable  of  fixing  more  than  a  minimal  amount  of  the  carbonic 
acid  of  the  blood. 

The  alkaline  phosphates  of  plasma,  which  are  capable  of  con- 
version into  acid  phosphates  by  association  with  carbonic  acid,  were 
again  erroneously  credited  with  too  much  importance  (Fernet). 
We  saw  in  fact  (p.  139)  that  the  main  part  of  the  phosphoric 
anhydride  found  in  the  ash  of  plasma  is  derived  from  combustion 
of  the  lecithin  and  nucleo-alburums,  and  that  normal  plasma  con- 
tains only  the  merest  trace  of  sodic  phosphate  (Sertoli). 

On  the  other  hand,  according  to  the  observations  of  Setschenow 
and  Torup,  maximal  importance  in  the  fixation  of  carbonic  acid 
must  be  assigned  to  the  globulins  of  the  serum,  which,  by  acting 
as  weak  acids,  are  able  to  combine  with  the  alkalies  of  the  blood. 
When  the  tension  of  carbonic  acid  increases,  the  globulins  of  the 
alkalies  are  dis7ociated,  and  combine  with  the  carbonic  acid  to 
form  carbonates ;  when,  on  the  contrary,  the  tension  of  carbonic 
acid  falls  the  globulins  are  again  associated  with  the  alkalie5, 
leaving  the  C02  in  the  free  state. 

Since  carbonic  acid  is  also  found  in  the  corpuscles  of  the  blood 
in  a  readily  dissociable  form,  it  is  probable  that  the  combinations 
of  the  globulins  with  the  alkalies  exercise  the  same  office  in  the 
corpuscles  as  in  the  plasma,  in  the  dissociation  of  carbonic  acid. 
It  should,  however,  be  noted  that  the  absorption  of  the  latter,  as 
effected  by  the  corpuscles,  is,  in  comparison  with  absorption  in  the 

VOL.  I  2  c 


386  PHYSIOLOGY  CHAP. 

serum,  dependent  to  a  much  greater  extent  on  the  partial  pressure 
of  the  C02.  According  to  Bohr,  this  fact  depends  on  the  capacity 
of  the  haemoglobin  to  unite  chemically  not  only  with  the  oxygen, 
but  also  with  the  carbonic  acid.  He  further  showed  that  this  last 
combination  is  in  no  way  obstructed  by  the  simultaneous  combina- 
tion with  oxygen ;  which  leads  us  to  suppose  that  the  two  gases 
are  fixed  in  two  different  portions  of  the  haemoglobin  molecule,  i.e. 
the  oxygen  in  the  iron-containing  portion  of  the  colouring  matter, 
the  carbonic  acid  in  the  protein  residue  (Fig.  169). 

According  to  Fredericq  the  non -coagulated  venous  blood  of  the 
horse  is  capable  of  absorbing  71 '4  vols.  per  cent  of  carbonic  acid, 
while  the  mass  of  corpuscles  from  the  same  animal  only  absorbs 


FIG.  169.— Curve  of  absorption  of  CO2,  by  1-76  per  cent  solution  of  haemoglobin  (dotted  line),  and 
by  one  of  3'8  per  cent  (unbroken  line)  in  relation  to  progressive  increase  of  pressure.  (Bohr.)  The 
pressure  (in  mm.  Hg)  is  recorded  along  the  axis  of  the  abscissae  ;  the  amount  of  CO2  (in  c.c.) 
absorbed  by  1  grm.  haemoglobin,  along  the  axis  of  the  ordinates. 

49 -6  vols.  per  cent.  It  follows  that  the  amount  of  CO2  fixed  by  the 
plasma  is  greatly  in  excess  of  that  fixed  by  the  corpuscles. 

The  carbonic  acid  of  the  serum,  according  to  the  unanimous 
results  of  Fredericq,  Zuntz,  and  Alex.  Schmidt,  is  about  86  per 
cent  of  that  contained  in  the  whole  of  the  blood.  It  is  possible, 
however,  that  in  the  process  of  defibrination,  part  of  the  carbonic 
acid  of  the  corpuscles  may  pass  into  the  serum,  and  that  under 
normal  conditions  the  gas  content  of  the  blood  is  divided  in 
different  proportions  between  the  corpuscles  and  the  plasma. 
Certain  experiments  of  Hamburger  show,  indeed,  that  by  merely 
changing  the  amount  of  gases  in  the  blood,  some  individual  sub- 
stances may  pass  from  the  plasma  to  the  corpuscles,  and  from 
the  corpuscles  to  the  plasma: 

Another  notable  fact  is,  that  by  means  of  the  Torricellian 
vacuum,  it  is  possible  to  extract  from  the  blood  the  whole  of  the 
carbonic  acid  which  it  holds  in  combination  (Setschenow).  From 


xi  EESPIKATOEY  EXCHANGES  387 

serum,  on  the  contrary,  with  the  simple  vacuum,  it  is  only  possible 
to  extract  one  part,  and  the  addition  of  a  weak  acid  is  required  to 
extract  the  residue,  which  is  more  stably  combined,  and  is  present 
in  the  blood  to  the  amount  of  5-9  vols.  per  cent  (Pfiliger).  The 
fact  that  this  portion  also  is  turned  out,  in  vacuo,  in  the  presence 
of  corpuscles,  without  adding  acid,  suggests  that  the  corpuscles 
contain  substances  that  function  as  acids,  and  that  these  are 
diffused  into  the  plasma  during  the  action  of  the  vacuum,  or  that 
th$  sodic  carbonate  of  the  plasma  penetrates  to  the  corpuscles. 
Among  the  acids  of  the  corpuscles  the  first  place  must  be  given  to 
phosphoric  anhydride,  which  they  contain  in  larger  quantities  than 
the  plasma;  besides  which  the  oxyhaemoglobin  functions  as  an 
acid,  as  was  demonstrated  by  Preyer,  since  it  is  capable  of  liberat- 
ing carbonic  acid  from  its  sodium  combinations  in  vacuo. 

In  regard  to  nitrogen  and  argon,  we  must 'confine  ourselves  to 
saying  that  these  gases  are  found  in  the  blood  in  amounts  differing 
little  from  those  in  which  they  are  absorbed  and  dissolved  by 
watery  fluids  in  the  presence  of  atmospheric  air.  According  to 
Kegnard  and  Schloesing,  about  0'04  vol.  per  cent  of  the  2  vols.  per 
cent  of  indifferent  gases  extracted  from  the  blood  are  argon.  The 
opinion  held  by  some  that  a  small  amount  of  free  nitrogen  is 
developed  during  the  oxidative  processes  of  the  nitrogenous 
substances  of  the  tissues,  and  is  subsequently  poured  into  the 
blood,  has  not  at  present  been  confirmed  by  any  incontrovertible 
evidence.  Regnault  and  Keiset  found  a  slight  increase  of  nitrogen 
in  expired  as  compared  with  inspired  air.  So,  too,  the  nitrogen 
extractible  from  venous  blood  is  always  somewhat  greater  than 
that  which  can  be  extracted  from  arterial  blood.  Pettenkofer 
and  Voit  gave  an  adequate  explanation  of  these  facts,  on  the 
assumption  that  they  depend  on  the  swallowing  of  air  with 
the  food,  and  on  the  absorption  of  the  nitrogen  contained  in  the 
gases  of  the  intestines. 

VIII.  Since  both  oxygen  and  carbonic  acid  are  thus  found  in 
the  blood  in  the  form  of  readily  dissociable  combinations  (in 
relation  to  variations  of  partial  pressure),  it  is  natural  to  conclude 
that  the  gas  exchanges  which  take  place  incessantly  between  the 
blood  circulating  through  the  capillaries  of  the  lungs  and  the  air 
contained  in  the  pulmonary  alveoli  (external  respiration)  are 
accomplished  by  a  simple  physical  process  of  diffusion,  regulated 
by  Dalton's  law.  They  depend,  i.e.,  on  the  difference  of  the  partial 
pressures  of  the  said  gases  as  contained  in  the  fluid  and  gaseous 
media,  separated  by  permeable  septa  or  membranes,  formed  by  the 
walls  of  the  capillaries  and  the  epithelial  cells  that  line  the  alveoli. 

The  scientific  demonstration  of  this  theory  involved  a  series  of 
researches,  directed  to  the  separate  determination  of  the  partial 
pressures  of  the  two  gases  in  venous  and  in  arterial  blood,  in  order 
to  compare  them  with  those  of  inspired  and  expired  air. 


388 


PHYSIOLOGY 


CHAP. 


Ill  older  to  determine  the  tension  or  partial  pressure  of  the  (X  or  GO._,  of 
the  air  (at  0°  C.,  and  mean  pressure  of  760  mm.  Hg)  it  is  sufficient  to  know 


FiO.  170.  —  Pfli'ger's  pulmonary  catheter,  modified  by  Ludwig. 

its  percentage  composition.  Since  inspired  air  con- 
tains 20-96  per  cent  of  O2  and  OO3  per  cent  of 
OCX,  the  partial  pressure  of  the  O2=159'3  mm.  Hg, 
and  that  of  the  C02  =  0-228  mm.  Hg.  To  deter- 
mine the  tension  of  the  gases  of  expired  air, 
whether  emitted  from  the  trachea,  or  at  a  deeper 
level  where  it  bifurcates  with  the  bronchi,  it  is 
sufficient  to  determine  the  percentage  composition 
of  the  0.,  and  CO.,  in  the  air  obtained  during  ex- 
piration by  an  air-pump  attached  to  a  simple 
sound,  the  end  of  which  can  be  introduced  more 
or  less  deeply  into  the  respiratory  passages. 

It  is,  on  the  contrary,  difficult  to  determine 
exactly  tlie  tension  of  the  02  and  CO.,  of  the  cir- 
culating blood,  venous  or  arterial.  Indirect  methods 
have  to  be  employed  for  this  purpose. 

Pfliiger  and  Wolffberg,  to  determine  the  tension 
of  O.,  and  C0.2  in  venous  blood  circulating  in  the 
pulmonary  capillaries,  devised  the  method  of  sound- 
ing the  lung  by  a  very  simple  instrument,  which 
they  called  the  pulmonary  catheter  (Fig.  170).  It 
consists  of  two  elastic  tubes,  the  finer  of  which  is 
inserted  into  the  larger.  The  first  has  an  open  end, 
intended  to  communicate  with  one  of  the  bronchi, 
from  which  air  can  be  aspirated  by  means  of  the 
Torricellian  vacuum  at  the  other  end.  The  second 
is  closed,  and  terminates  in  a  thin  rubber  balloon, 
which  can  be  easily  inflated  by  a  small  bellows. 

Having  opened  the  trachea  of  a  dog,  the  sound 
is  introduced  into  the  bronchus  leading  to  the 
inferior  left  lobe  of  the  lung ;  the  small  terminal 
vesicle  of  the  external  tube  is  then  inflated,  so  that 
it  hermetically  seals  the  bronchus  into  which  it  is 
introduced,  and  makes  the  corresponding  lobe  of 
the  lung  impervious  to  external  air,  which  does 
not  appreciably  disturb  the  respiratory  movements  of  the  animal.  After 
four  to  five  minutes  the  air  contained  within  the  blocked  lobe  of  the  lung 


FIG.  171. — Frederick's  aero- 
tonometer.  The  blood, 
which  is  rendered  inco- 
agulable with  peptone, 
rises  from  the  carotid  in 
tube  (i ;  spreads  over  sur- 
face of  larger  tube  c,  where, 
by  diffusion,  it  is  brought 
into  equilibrium  of  tension 
with  the  mixture  of  gases 
therein  contained  ;  and  re- 
turns by  the  jugular  vein 
into  the  animal  by  tube  b. 
Tube  c  is  covered  with  a 
large  tube  R,  within  which 
water  at  the  temperature 
of  the  animal's  body  is 
kept  continuously  circu- 
lating. The  small  lateral 
tube  t  introduces  the 
artificial  mixture  of  gases 
into  tube  c  at  the  com- 
mencement of  the  experi- 
ment. The  thermometer 
T  regulates  temperature 
of  water  circulating  in  R 
during  the  experiment. 


xi  RESPIRATORY  EXCHANGES  389 

is  again  in  equilibrium  with  the  tension  of  the  gases  of  the  venous  blood 
circulating  in  it.  The  air  is  then  aspirated  from  the  sound,, and  its  percentage 
composition  determined  by  Bunseii's  method. 

The  values  found  for  the  CO2  and  O^  tension  indirectly  indicate  the 
tension  of  these  gases  in  the  venous  blood  circulating  in  the  capillaries  of  the 
lungs. 

The  tension  of  the  02  and  C02  of  arterial  blood  is  determined  by  means 
of  the  so-called  aerotonometers.  The  simplest  form  is  that  of  Fredericq, 
represented  in  Fig.  171.  It  consists  of  a  glass  tube,  filled  with  a  gaseous 
mixture  of  known  composition  (10  per  cent  of  02,  5  per  cent  C02,  and  the 
rest  N),  along  the  internal  surface  of  which  there  is  a  constant  flow  of  blood 
from  the  carotid  artery.  During  its  passage  through  the  tube,  the  tensions 
of  the  blood-gases  and^of  the  artificial  mixture  of  gases  are  equilibrated. 

By  making  the  blood  incoagulable  through  previous  injection  of  pro- 
peptone  or  albumose,  and  returning  to  the  circulation  by  the  jugular  vein  the 
blood  that  left  by  the  carotid,  the  experiment  can  be  prolonged  for  a 
considerable  time  (an  hour  or  more),  so  as  to  be  certain  of  having  established 
equilibrium  of  tension  between  the  gases  of  the  arterial  blood  and  those 
contained  in  the  aerotonometer.  The  blood  that  flows  through  the  instrument 
is  maintained  at  body  temperature  by  means  of  an  external  glass  jacket  in 
which  water  is  circulated  at  the  required  temperature.  When  the  experiment 
is  completed,  the  percentage  composition  of  the  mixture  of  gases  in  the 
aerotonometer  is  calculated  by  the  usual  method,  and  the  values  obtained 
express  the  partial  pressure  of  the  O.>  and  C(X  of  arterial  blood. 

The  experiments  on  the  tension  of  the  respiratory  gases  have 
not  led  to  uniform  results  :  they  vary  greatly  even  in  the  same 
animals  under  slightly  different  conditions. 

The  following  table  gives  the  average  values  cited  by  F. 
Schenck  and  A.  Giirber  in  their  Text- Book  of  Human  Physiology 
(1897), which  all  relate  to  experiments  carried  out  on  dogs: — 


At  0°  C.  and  760 
mm.  Hg. 

Inspired  Air. 

Expired  Air. 

Arterial  Blood,     i     Venous  Blood. 

mm.  HX- 

mm.  H-. 

mm.  H#.                   mm.  H<,r. 

Oxygen     . 

150 

122 

29'6 

21-0 

Carbonic  Acid  . 

0-3 

30 

22-0 

41-0 

These  data  coincide  perfectly  with  the  theory  which  holds 
the  respiratory  gas  exchanges  to  be  the  effects  of  simple 
diffusion,  which  causes  the  gases  to  pass  from  the  point  of  greater 
to  that  of  less  tension.  In  fact  the  tension  of  O9  is  seen  to 
diminish  from  inspired  to  expired  air,  and  from  that  to  arterial 
blood ;  and  the  tension  of  C0.7  diminishes  from  venous  blood  to 
that  of  expired  air,  and  thence  to  that  of  inspired  air.  The 
oxygen  must  therefore  be  absorbed  by  diffusion  from  the  respiratory 
passages  into  the  arterial  blood,  while  the  carbonic  acid  must  be 
exhaled  by  diffusion  from  the  venous  blood  into  the  respiratory 
passages. 

The  results  of  Bohr's  subsequent  experiments  do  not,  however, 
agree  with  this  theory.  •  With  one  of  his  special  aerotonometers 


390  PHYSIOLOGY  CHAP. 

he  determined  the  tension  of  the  gases  in  the  circulating  arterial 
blood,  and  that  of  the  expired  air  at  the  tracheal  bifurcation. 
He  repeatedly  found  that  the  partial  pressure  of  the  carbonic  acid' 
of  the  blood  was  less,  and  that  of  the  oxygen  greater,  than  the 
respective  partial  pressures  of  the  two  gases  in  expired  air. 

In  some  of  Bohr's  experiments,  for  instance,  the  partial  pressure 
of  the  O2  and  C02  varies  as  follows : — 

02  of  arterial  blood =  100-144  mm.  Hg. 

Og  of  expired  air,  at  tracheal  bifurcation  .        .  =   95-130        „ 

C02  of  arterial  blood =    17-30 

C02  of  expired  air,  at  tracheal  bifurcation         .  =   35-  41        „ 

Against  these  results  of  Bohr,  the  objection  that  he  did  not  allow 
sufficient  time  for  equilibrium  of  tension  to  be  established  between 
the  gases  of  the  arterial  blood  and  the  artificial  air  contained  in 
the  aerotonometer,  has  no  weight,  because  in  this  air,  before  the 
entrance  of  the  arterial  blood,  the  partial  pressure  of  the  02  was 
less,  and  that  of  the  CO2  was  greater,  than  after  the  experiment. 
On  the  basis  of  these  facts,  which  are  opposed  to  the  theory  of 
diffusion  as  the  sole  determinant  of  pulmonary  gas  exchanges, 
Bohr  puts  forward  the  hypothesis  that  the  walls  of  the  pulmonary 
alveoli  function  as  a  secreting  gland,  and  that  the  cells  that  line 
them  are  capable  of  actively  absorbing  oxygen  and  exhaling 
carbonic  acid,  even  against  the  laws  of  the  diffusion  of  gases. 

Fredericq  in  his  latest  work  does  not  accept  Bohr's  conclusions. 
He  invariably  finds  the  tension  of  oxygen  in  the  arterial  blood 
to  be  less,  and  that  of  carbonic  acid  greater,  than  the  respective 
tensions  of  the  two  gases  in  alveolar  air.  But  this  (as  Tigerstedt 
has  pointed  out)  does  not  contradict  the  phenomena  observed 
by  Bohr.  One  single  fact,  determined  under  valid  experimental 
conditions  to  be  irreconcilable  with  the  exclusive  theory  of 
diffusion,  gives  legitimate  reason  to  suspect  that  other  forces 
intervene  in  the  production  of  gas  exchanges,  and  are  capable  of 
accelerating  the  effects  of  diffusion,  and  even  of  acting  in 
opposition  to  its  laws.  The  study  of  this  interesting  question 
deserves  to  be  pursued  without  prejudice,  the  more  so  as  Bohr 
has  discovered  another  fact  that  appears  to  be  of  the  utmost 
importance.  After  collecting  and  analysing  the  gases  contained  in 
the  swim-bladder  of  certain  fishes  caught  at  a  great  depth,  he 
found  them  to  contain  as  much  as  80  per  cent  oxygen.  On 
puncturing  and  emptying  the  swim-bladder,  he  found  that  it  filled 
anew  with  oxygen,  but  only  on  condition  that  the  nerve  plexuses 
leading  to  it  were  spared.  Once  this  fact  is  admitted,  the 
legitimate  conclusion  must  be  that  the  cells  lining  the  swim- 
bladder  (which  may  be  regarded  as  a  modified  lung)  function  as 
glandular  elements  secreting  oxygen  under  the  influence  of  the 
nervous  system,  and  contrary  to  the  laws  of  diffusion ;  just  as  the 


xi  KESPIRATOKY  EXCHANGES  391 

salivary  cells,  in  obedience  to  nervous  impulses,  secrete  saliva  in 
defiance  of  a  counter-pressure  greater  than  that  of  the  arterial  blood 
circulating  in  the  gland  (Ludwig). 

Haldane  and  Smith  (1896)  investigated  the  tension  of  oxygen 
in  the  pulmonary  blood  by  a  method  applicable  to  man.  The 
method  is  based  on  the  fact  already  demonstrated  by  Haldane  in 
1895,  that  with  simultaneous  action  of  oxygen  and  carbonic  oxide 
on  the  blood,  the  amount  of  the  carbonic  oxide  fixed  by  the  blood 
is. proportional  to  the  oxygen  tension,  so  that  it  is  possible  from 
the  degree  of  absorption  of  carbonic  oxide  in  the  blood  to  calculate 
the  tension  of  the  oxygen  present.  If  a  man  or  other  animal  is 
made  to  breathe  a  gaseous  mixture  containing  a  small  quantity 
(exactly  determined)  of  CO  for  a  time  long  enough  to  make  the 
carbonic  oxide  content  constant  in  the  blood  (measuring  it  at 
intervals  by  small  samples  of  blood  taken  from  the  subject),  it  is 
possible  from  the  degree,  thus  measured,  of  fixation  of  CO  by  the 
blood,  to  calculate  the  02  tension  that  prevails  in  the  pulmonary 
blood.  It  results  from  these  experiments  that  the  O2  tension 
in  the  blood  of  a  man's  lungs  amounts  to  26'2  hundredths  of  an 
atmosphere  equal  to  200  mm.  Hg,  a  figure  that  is  inexplicable  on 
the  hypothesis  of  simple  gas  diffusion  as  the  cause  of  the  absorption 
of  oxygen  in  the  lung.  Identical  results  were  obtained  from 
experiments  on  birds  and  mice  (1897),  by  means  of  which  these 
authors  were  also  able  to  show  how  want  of  oxygen  acted  as  a 
stimulus  to  tjie  active  absorption  of  this  gas  by  the  pulmonary 
epithelium. 

With  regard  to  the  process  of  the  elimination  of  C0.7  from  the 
lungs  in  the  air  of  the  pulmonary  alveoli,  Grandis  (19130)  called 
attention  to  a  new  factor  which  had  till  then  escaped  the  notice  of 
physiologists. 

It  is  known  that  in  addition  to  C02,  a  considerable  amount  of 
water-vapour  is  eliminated  by  the  expired  air  from  the  blood 
plasma  circulating  through  the  lung  (according  to  Loewy,  alveolar 
air  contains  about  6  per  cent  of  aqueous  vapour).  The  blood 
accordingly  undergoes  a  temporary  increase  of  concentration 
during  its  passage  through  the  lungs,  which,  by  raising  the  C02 
tension,  must  facilitate  its  expulsion  into  the  alveolar  air. 
Grandis  confirmed  the  importance  of  this  fact  by  certain  experi- 
ments in  vitro,  in  which  he  artificially  increased  the  concentra- 
tion of  the  blood,  by  adding  strong  solutions  of  sodium  chloride 
and  sugar,  with  the  effect  of  a  prompt  rise  of  tension  in  the  gases 
of  the  blood. 

On  the  ground  of  these  experiments  he  thinks  it  probable  that 
in  living  animals  also  the  greater  concentration  of  the  blood,  on 
evaporation  of  the  water  in  the  pulmonary  alveoli,  must  facilitate 
the  expulsion  of  C02.  JThe  experiments  of  Grandis,  however,  show 
that  the  greater  concentration  of  the  blood  raises  the  tension,  not 


392  PHYSIOLOGY  CHAP. 

only  of  the  C02,  but  also  of  the  02,  and  thus  can  have  no  appreciable 
value  as  a  factor  in  the  pulmonary  gas  exchanges — seeing  that  if 
on  the  one  hand  it  facilitates  the  elimination  of  C02  from  the 
blood,  it  checks  the  absorption  of  O2  on  the  other. 

Another  question  indirectly  connected  with  the  nature  of  the 
pulmonary  gas  exchanges,  is  that  which  refers  to  the  influence 
which  is,  or  can  be,  exercised  upon  them  by  the  nervous  system. 

At  the  end  of  1892,  Henriques  demonstrated  experimentally 
in  rabbits  and  dogs  that  stimulation  of  both  vagi  might  cause 
variations  in  the  respiratory  gas  exchanges  of  the  lungs.  These 
experiments  were  taken  up  by  Maar  in  1902,  and  extended  both 
to  cold-blooded  animals  (tortoises)  and  to  the  warm-blooded 
(rabbit).  He  endeavoured  to  define  the  precise  effect  of  section 
and  artificial  stimulation  of  the  vagus  and  sympathetic  upon  the 
pulmonary  gas  exchanges.  The  experiments  on  cold-blooded 
animals  led  to  the  conclusion  that  absorption  of  oxygen  by  the 
lungs  was  under  the  influence  of  the  nervous  system,  the  vagus 
containing  both  nerve  fibres  that  increase  the  absorption  of 
oxygen,  and  also  other  fibres  that  dimmish  it.  The  former  run  to 
the  lung  of  the  opposite  side,  the  latter  to  that  of  the  same  side. 
It  was  found  impossible  to  establish  any  direct  influence  of  the 
sympathetic  on  respiratory  pulmonary  exchanges,  nor  did  the 
experiments  on  warm-blooded  animals  lead  to  any  definite  or 
concordant  results.  The  demonstration  of  a  direct  influence  of 
the  nervous  system  on  the  pulmonary  gas  exchanges  tells  in  favour 
of  Bohr's  theory. 

In  speaking  of  recent  work  on  this  subject,  mention  must  be 
made  of  Krogh  (1904),  who  studied  the  cutaneous  and  pulmonary 
respiration  of  the  frog,  and  came  to  the  conclusion  that  cutaneous 
respiration  (which  serves  especially  for  elimination  of  carbonic 
acid)  is  independent  of  the  nervous  system,  and  can  be  explained 
on  purely  physical  grounds  (gaseous  diffusion),  while  pulmonary 
respiration  (which  particularly  controls  the  absorption  of  oxygen) 
is,  on  the  contrary,  effected  principally  by  secretory  processes  of 
the  epithelium,  and  is  regulated  by  the  nervous  system. 

On  the  other  hand,  Loewy  and  Zuntz  in  their  latest  publication 
(1904)  still  contend  that  the  laws  of  diffusion  adequately 
account  for  the  gas  exchanges  between  the  alveolar  air  and  the 
blood.  They  determined  the  velocity  with  which  carbonic  acid 
traverses  an  excised  frog's  lung,  and  from  this,  taking  into  account 
the  varying  thickness  of  the  pulmonary  walls,  deduced  the  con- 
ditions of  gas  diffusion  in  the  human  lung.  They  conclude  that 
the  conditions  of  diffusion  for  the  passage  of  oxygen  from  the 
pulmonary  alveoli  to  the  blood,  and  thence  to  the  tissues,  are  so 
favourable  that  they  ensure  more  than  sufficient  absorption  of 
oxygen,  even  in  the  most  extreme  cases  of  rarefaction  of  air  com- 
patible with  life. 


xi  EESPIKATOEY  EXCHANGES  393 

IX.  We  know  very  little  as  yet  about  the  physico-chemical 
processes  which  complete  the  gas  exchanges  between  the  blood 
circulating  in  the  aortic  capillaries,  and  the  living  cells  of  the 
tissues,  by  the  agency  of  the  interstitial  lymph  (internal 
respiration). 

It  was  formerly  supposed  that  the  transformation  of  arterial 
into  venous  blood  took  place  within  the  capillaries.  But  there  are 
well-ascertained  facts  which  prove  the  blood,  when  extracted  and 
kept  at  body  temperature,  not  to  be  the  seat  of  any  very  energetic 
oxidative  phenomena.  The  oxygen  it  contains  gradually  dis- 
appears, i.e.  drawn  arterial  blood  slowly  becomes  venous.  On  the 
other  hand,  circulating  arterial  blood  is  known  not  to  become 
venous  along  the  entire  course  of  the  aortic  system,  but  only  when 
it  is  passing  through  the  capillaries.  This  fact  was  explained  on 
the  hypothesis  that  the  intermediate  products  of  tissue  consumption, 
which  reach  the  arterial  blood  by  the  capillaries,  consisted  of 
reducing  substances,  i.e.  are  avid  of  oxygen,  which  they  rapidly 
subtract  from  the  oxyhaemoglobin.  This  supposition  is  no 
longer  admissible,  since  it  has  been  demonstrated  that  only  the 
erythrocytes,  not  the  blood  plasma,  nor  the  lymph  of  asphyxiated 
animals  (in  which  there  must  be  an  accumulation  of  many 
reducing  substances),  are  capable  of  chemically  combining  with 
oxygen.  Neither  the  blood  plasma,  then,  nor  the  lymph,  contain 
reducing  substances,  since  the  latter  do  not  pass  into  these  fluids, 
but  arise  in  the  living  cells  of  the  tissues  which  breathe  in  virtue 
of  their  metabolism,  i.e.  they  take  up  oxygen  and  give  otf  carbonic 
acid.  It  is  therefore  evident  that  the  tissues  are  the  seat  of 
internal  respiration,  and  if  the  blood  also  breathes,  however  slowly, 
this  is  in  virtue  of  the  mass  of  corpuscles  which  it  contains,  and 
by  which  it  functions  as  a  tissue. 

Many  direct  proofs  might  be  adduced  as  to  the  correctness  of 
this  theory.  When  fragments  of  living  tissue,  particularly  of 
muscle,  are  dissolved  in  drawn  arterial  blood  or  in  a  solution  of 
oxyhaemoglobin,  a  rapid  reduction  follows,  by  which  the  oxyhae- 
moglobin is  promptly  converted  into  haemoglobin  in  that  portion 
of  the  fluid  which  immediately  surrounds  the  fragments  (Hoppe- 
Seyler).  If  benzylic  alcohol  or  salicylic  aldehyde  are  added  to 
the  arterial  blood  drawn  from  the  vessels,  it  does  not  oxidise  to 
any  appreciable  extent ;  if,  on  the  other  hand,  this  blood,  plus  one 
of  the  above  substances,  is  circulated  in  the  vessels  of  organs 
recently  extracted  from  a  living  animal  (kidney  or  lung),  consider- 
able quantities  of  benzoic  or  salicylic  acid  are  at  once  produced 
by  oxidation  (Schmiedeberg).  The  oxidation  performed  by  the 
isolated  surviving  organ  seems  due  to  the  action  of  special  enzymes 
contained  within  the  cells  of  the  tissues  (Schmiedeberg,  Jacquet, 
Buchner). 

All  tissues  breathe  (Paul  Bert),  but  it  is  particularly  in  muscle 


394  PHYSIOLOGY  CHAP. 

that  the  oxidising  processes  acquire  a  greater  degree  of  intensity, 
and  have  been  most  studied.  Active  muscle  breathes  in  excess  of 
resting  muscle.  Blood  coming  from  the  vein  of  a  tetanised  muscle 
is  dark  in  colour,  and  contains  a  minimal  amount  of  oxyhaemo- 
globin  ;  while  the  blood  which  comes  from  a  muscle  that  is  resting, 
or  paralysed  by  section  of  its  motor  nerve,  presents  the  normal 
characters  of  venous  blood,  in  which — as  we  have  seen — the  oxygen 
content  may  exceed  15  vols.  per  cent  of  the  blood. 

Again,  when  muscle  is  placed  under  conditions  that  prevent  it 
from  absorbing  oxygen,  e.g.  when  it  is  brought  into  an  atmosphere 
of  hydrogen  or  nitrogen,  it  continues  to  give  off  carbonic  acid,  and 
for  a  certain  time  is  capable  of  contracting  (Hermann,  see  p.  68). 
It  would  thus  seem  that  muscle  must  be  allowed  the  property  of 
taking  up  and  storing  oxygen  in  such  a  condition  that  it  cannot 
be  removed  by  simple  lowering  of  pressure.  The  oxygen  required 
for  the  formation  of  carbonic  acid,  given  off  by  muscle  in  the 
presence  of  nitrogen  and  hydrogen,  is  certainly  derived  from  that 
previously  stored  up  and  fixed  in  a  compound  similar  to,  but  more 
stable  than,  that  into  which  it  enters  with  haemoglobin,'  and  which 
has  been  wrongly  termed  intermolecular  oxygen. 

According  to  recent  work  of  Verworn,  Baglioni,  and  H. 
Winterstein  (1900-1907),  the  tissue  whose  vitality  is  most  strictly 
associated  with  the  action  of  free  oxygen  is  the  central  nervous 
system.  Baglioni,  e.g.,  found  on  isolating  the  frog's  spinal  cord 
from  the  body  after  cutting  out  the  circulation,  and  taking  as  the 
index  of  its  activity  the  reflex  movements  of  a  posterior  limb, 
connected  with  the  cord  by  the  sciatic  nerve,  that  the  reflex 
activity  of  the  cord  is  in  strict  ratio  with  the  O9  tension  of  the 
surrounding  atmosphere.  If  placed  in  a  moist  chamber,  through 
which  nitrogen  is  passed  without  a  trace  of  oxygen,  such  a  spinal 
cord  at  a  temperature  of  15-20C  0.  ceases  to  exhibit  reflexes  after, 
half  to  three-quarters  of  an  hour.  If  it  is  then  suddenly  brought 
back  into  the  presence  of  oxygen,  it  recovers  its  vitality.  On  the 
other  hand,  Baglioni  succeeded  in  keeping  alive  the  isolated  spinal 
cord  of  amphibia  for  a  comparatively  long  period  (forty-eight  hours 
and  more)  by  placing  it  in  a  warm  chamber  through  which  pure 
oxygen  was  circulated.  This  specifically  high  demand  of  the  central 
nervous  system  for  oxygen  explains  the  fact  that  in  all  cases  of 
asphyxia  or  lack  of  oxygen  in  tlie  blood,  the  first  tissue  that  feels 
the  toxic  effects,  and  ceases  its  activities,  is  the  central  nervous 
system  (cerebral  cortex,  spinal  cord ;  see  p.  70).  We  shall  return 
to  this  subject  in  Vol.  III.,  in  treating  of  the  physiology  of  the 
nervous  system. 

Moleschott  enunciated  the  hypothesis  that  the  oxygen  passing 
from  the  blood  to  the  tissues  is  utilised  in  the  constructive  pro- 
cesses, i.e.  it  enters  into  the  most  complex  substances  of  the  tissues, 
which  then,  on  splitting  up,  generate  carbonic  acid.  Cl.  Bernard 


xi  EESPIKATOKY  EXCHANGES  395 

also  admits  that  "  the  oxygen  combines  in  some  way  with  the 
tissues  so  as  to  constitute  a  provision  for  use  when  the  animal  is 
unable  to  procure  it  from  without."  He  based  this  assumption 
particularly  on  the  fact  that  muscle  absorbs  more  oxygen  during 
rest,  and  spends  more  during  activity,  as  though  it  accumulated 
reserves  to  expend  lavishly  when  need  arises.  Nothing  definite  is 
known,  however,  as  to  the  nature  of  the  probable  combinations 
formed  by  oxygen  with  the  different  materials  for  building  up 
muscles  and  other  tissues,  or  of  the  intermediate  anabolic  and 
katabolic  forms,  through  which  it  passes  in  combining  with  carbon 
into  carbonic  acid.  "  The  whole  mystery  of  life,"  says  Foster, 
"  lies  hidden  in  the  story  of  that  progress,  and  for  the  present  we 
must  be  content  with  simply  knowing  the  beginning  and  the 
end." 

We  know  that  carbonic  acid  is  one  of  the  ultimate  products  of 
the  katabolic  processes,  and  that  the  variations  in  the  amount 
formed  and  eliminated  by  the  tissues  are,  as  Fano  says,  an 
expression  "  of  corresponding  changes  in  the  course  of  the 
destructive  processes.  The  assimilated  oxygen  011  the  contrary 
enters,  at  least  in  part,  into  the  molecular  structure  of  our  tissues, 
is  included  in  the  series  of  synthetic  processes,  and  may  partially 
be  considered  #s  an  element  which  contributes  to  the  anabolic  or 
constructive  processes."  We  shall  return  to  this  argument  in 
treating  of  the  metabolism  or  material  exchanges  of  the  body  as  a 
whole. 

In  regard  to  this  subject  of  the  respiratory  gas  exchanges 
between  the  blood  and  the  tissues,  the  facts  observed  by  Pfliiger 
and  Strassburg,  to  the  effect  that  the  lymph,  serous  fluids,  and 
certain  secretions  (bile,  urine,  saliva,  milk)  formed  within  the 
living  tissues  contain  merely  a  trace  of  oxygen,  and  a  comparatively 
large  amount  of  carbonic  acid,  are  very  remarkable.  These  authors 
conclude  that  02  tension  is  low  or  practically  nil  in  the  tissues, 
while  the  C02  tension  on  the  contrary  is  high. 

The  high  tension  of  carbonic  acid  that  prevails,  according  to 
recent  researches,  in  living  tissues  is  of  especial  significance, 
because  it  facilitates  the  dissociation  of  oxygen  from  oxyhaemo- 
globin,  and  thus  places  at  the  disposal  of  the  tissues  the  maximum 
possible  amount  of  the  oxygen  received  from  the  blood.  Bohr, 
Hasselbach,  and  Krogh  (1904)  found  that  on  bringing  dog's  blood,  in 
vitro,  at  38°  C.  into  the  presence,  simultaneously,  of  02  at  low  tension 
(5  mm.  Hg),  and  of  C02  at  various  tensions,  the  blood  absorbs  a 
less  degree  of  02  than  when  it  is  in  presence  of  02  alone,  and  that 
the  decrease  in  absorption  is  proportional  to  the  amount  of  CO2 
simultaneously  present. '  This  influence  is  much  less  felt  if  the  O2 
tension  is  progressively  raised,  as  is  clearly  shown  on  the  diagram 
(Fig.  172). 

The  physiological  value  of  this  fact  will  be  readily  appreciated. 


396  PHYSIOLOGY  CHAP. 

Since  the  tension  of  the  carbonic  acid  constantly  increases  with 
the  passage  of  the  blood  into  the  aortic  capillaries,  this  must 
facilitate  the  dissociation  of  oxygen,  and  increase  its  concentration 
in  the  blood  plasma,  so  that  it  can  be  easily  absorbed  by  the 
endothelia  of  the  capillaries  and  the  tissue  cells.  The  increase  in 
tension  of  the  carbonic  acid  partly  compensates  for  the  diminished 
concentration  of  oxygen  in  the  plasma  due  to  its  consumption  by 
the  tissues.  This  regulation  is  of  especial  importance  in  asphyxia, 
when  the  oxygen  of  the  blood  is  much  attenuated. 

On  the  other  hand  the  high  tension  of  carbonic  acid  in  the 
pulmonary  capillaries  does  not  in  any  way  diminish  the  absorption 


40      50      60      70      80      00     100     110    120    130    140    150 


Fin.  17-2. — Curve  showing  influence  of  varying  quantity  of  COo  on  absorption  of  oxygen  at  different 
pressures,  from  delibrinated  dog's  blood  at  88°  C.  (Bohr,  Hasselbach,  and  Krogh).  The 
percentage  amount  of  oxygen  absorbed  is  marked  on  the  axes  of  the  ordinates  ;  the  different 
pressures  of  oxygen  in  mm.  Hg,  on  the  axes  of  the  abscissa,  while  the  different  pressures  of 
CO->  acting  simultaneously  in  the  pressure  of  biood,  are  indicated  above  the  respective  curves. 

of  oxygen,  for  which,  as  has  been  shown,  the  influence  of  carbonic 
acid  becomes  negligible  in  the  presence  of  high  oxygen  tensions. 

This  fact  suffices  to  explain  on  a  simple  process  of  diffusion 
the  gas  exchanges  between  the  blood  and  the  tissues,  by  which 
the  latter  continually  absorb  oxygen  and  give  off  carbonic  acid, 
converting  arterial  into  venous  blood.  The  data  in  regard  to 
external  respiration,  do  not,  however,  preclude  the  probability  that 
the  physical  laws  of  diffusion  may,  in  the  case  of  internal 
respiration  also,  be  modified  by  the  activity  of  the  cells  which 
build  up  the  walls  of  the  capillaries. 

X.  We  have  seen  that  Lavoisier  conceived  of  respiratory 
chemistry  as  a  slow  double  combustion  of  carbon  and  hydrogen 
by  which  are  formed  carbonic  acid  and  water.  He  was  the  first  to 
show  that  the  amount  of  O2  absorbed  exceeds  that  of  the  C02 
exhaled,  from  which  fact  he  deduced  the  formation  of  water. 


xi  RESPIKATOKY  EXCHANGES  397 

The  gas  exchanges  of  respiration  are,  however,  more  complicated, 
as  is  readily  seen  on  examining  the  changes  induced  in  external 
air  by  animal  respiration. 

Expired  air,  in  comparison  with  inspired  air,  presents  the 
following  differences  :— 

(a)  It  contains  5  vols.  per  cent  less  of  oxygen  (according 
to  Vierordt  16*033  vols.  per  cent  instead  of  20*95  vols.  per  cent). 

(6)  It  contains  a  considerable  amount  of  carbonic  acid  (from 
3;3-5'5  vols.  per  cent,  according  to  Vierordt). 

(c)  According  to  Regnault  and  Reiset,  and  Seegeii  and  Nowak, 
expired  air  contains  a  slight  excess  of  nitrogen,  but  whether  this 
is  a  waste  product  from  the  tissues  owing  to  decomposition  of 
protein  is  doubtful,  as  already  stated ;    more  probably  it  comes 
from  absorption  in  the  blood  of  the  excess  nitrogen  contained  in 
the  intestinal  gases. 

(d)  It   contains    traces   of   free    hydrogen,   of   marsh   gas,   of 
ammonia,  and  of  other  gases  of  hitherto  unknown  composition. 
It  is  certain  that  these  substances  arise  partly  from  the  absorption 
of  intestinal  gases,  partly  from  exhalations  of  putrefactive  excreta 
that  clog  the  skin  and  integuments  (Hermann,  1883),  partly  from 
pulmonary  exhalations  which  when  collected  and  condensed  in 
sterilised   water,   and   inoculated    subcutaneously,    have   a    toxic 
action  (Brown-Sequard  and  D'Arsonval).     Eormanek  has  recently 
(1900)  occupied   himself   exclusively  with   the   question    of   the 
toxicity  of  expired  air.     He  found  that  air  passed  by  the  method 
of  Brown-Sequard   and   D'Arsonval   through   cages    of   animals 
contained  a   really  toxic   substance,  which    was   identified  with 
ammonia.     This   ammonia  was  not,  however,   derived   from,    the 
expired  air,  but  from  the  decomposition  of  urine  and  faeces  within 
the  cages.     When  this  source  of  impurity  was  eliminated,  expired 
air  was  obtained  which  had  no  toxic  action.     Formanek  concluded 
that  no  toxic  substances  were  developed  in  the  lungs  of  man  and 
other  healthy  animals.      The   sense   of  malaise  which   sensitive 
persons  experience  in  crowded  rooms  must  arise  reflexly,  from 
disturbance  of  thermal   regulation,  or   the   respiration   of  foul- 
smelling  substances. 

(e)  The  expired  air  is  saturated  or  nearly  so  with  the  aqueous 
vapour  exhaled  along  the  respiratory  passages. 

(/)  It  is  partly  deprived  of  the  dust,  and  the  germs  or 
sporules  that  are  never  absent  from  inspired  air,  and  which  are 
arrested  all  along  the  respiratory  tract  by  the  moisture  of  its  walls 
— these  being  clothed  with  vibratile  epithelia,  whose  function  is 
to  expel  them,  along  with  the  mucus  secreted  by  the  muciparous 
cells. 

(</)  Its  temperature  is  approximately  that  of  the  body 
(35-36°  C.),  consequently  its  volume  when  it  issues  from  the 
respiratory  passages  exceeds  that  of  the  inspired  air,  to  which  the 


398  PHYSIOLOGY  CHAP. 

aqueous  vapour  with  which  it  is  saturated  also  contributes. 
When  the  expired  air  is  again  reduced  to  the  temperature  and 
degree  of  moisture  of  that  inspired,  it  presents  in  relation  to  the 
latter  a  slight  diminution  of  volume,  as  first  noted  by  Lavoisier 
(1777). 

The  chemical  composition  of  expired  air  varies  between 
sufficiently  wide  limits,  not  merely  in  different  classes  and  species 
of  animals,  but  also  in  the  same  individual  under  different  external 
and  internal  conditions,  according  to  the  frequency  and  depth  of 
the  respiratory  movements.  The  slower  and  deeper  these  are,  the 
greater  will  be  the  output  of  carbonic  acid  and  intake  of  oxygen. 
The  first  portions  of  air  given  off  in  a  respiratory  act,  which  come 
from  the  more  superficial  bronchial  passages,  contain  less  carbon 
dioxide  and  more  oxygen,  in  comparison  with  the  later  portions  of 
expired  air,  which  come  from  the  deeper  bronchial  tubes  and  the 
alveoli. 

It  is  obvious  that  the  more  perfect  the  pulmonary  ventilation 
consequent  on  the  deepest  respiratory  acts,  the  more  rapid  and 
abundant  will  be  the  gas  exchanges,  and  therewith  the  emission  of 
carbonic  acid  and  absorption  of  oxygen  in  the  time  unit.  Ex- 
perience, however,  shows  that  increased  pulmonary  ventilation 
does  not  merely  increase  the  gas  exchanges,  which  would  be  a 
temporary  effect,  but  also  increases  the  formation  of  carbonic  acid, 
i.e.  the  absolute  quantity  which  is  expelled  in  the  unit  of  time. 
This  phenomenon  depends  on  the  fact  that  increased  pulmonary 
ventilation  exacts  more,  work  from  the  respiratory  muscles,  and 
naturally  determines  an  increase  of  combustion  and  thus  of 
carbonic  acid  production. 

When  a  known  volume  of  oxygen  is  converted  by  combustion 
into  carbonic  acid,  the  original  volume  of  gas  is  not  altered. 
Since,  however,  in  respiration  the  volume  of  oxygen  absorbed 
exceeds  that  of  carbonic  acid  exhaled,  it  follows  that  a  greater 
or  less  amount  of  oxygen  must  be  applied  to  other  oxidative 
purposes.  Among  these,  besides  the  combustion  of  hydrogen  by 
which  water  is  formed,  must  be  reckoned  the  combustion  of 
sulphur  to  form  sulphates,  and  of  phosphorus,  which  forms 
phosphates. 

The  ratio  between  the  volume  of  carbonic  acid  exhaled  and 
the  volume  of  oxygen  absorbed  is  known  as  the  respiratory 

CO 
quotient.    This  quotient,  expressed  by  the  formula   ~  2,  is  generally 

lower  than  1,  and  varies  considerably  in  the  different  classes  of 
animals,  and  even  in  the  same  individual,  according  to  the  nature 
of  his  food. 

In  the  combustion  of  the  different  food-stuffs  outside  the  body 
a  different  quantity  of  oxygen  is  required  according  to  the 
different  chemical  constitution  of  their  molecules.  Thus,  each 


xi  KESPIEATOKY  EXCHANGES  399 

molecule  of  the  substances  comprised  in  the  carbo-hydrate  group 
contains  oxygen  enough  to  convert  the  whole  of  the  hydrogen  into 
water.  Accordingly  for  their  complete  combustion  the  only 
oxygen  required  is  that  necessary  for  conversion  of  the  carbon 
into  carbonic  acid.  Hence  the  volume  of  CO.,  formed  is  perfectly 

CO 
equal  to  the  volume  of  02  consumed,  the  quotient   Q  2  =  1. 

For  the  perfect  combustion  of  fats  and  proteins,  on  the 
contrary,  more  O.7  is  required,  since  in  their  molecules  there  is  not 

CO 
enough  O0  to  convert  all  the  H2  into  water.     The  quotient  -~- a 

is  therefore  less  than  1.  In  the  complete  combustion  of  fats,  the 
quotient  =0'7l  ;  in  the  complete  combustion  of  proteins  =  0'78. 

It  follows  that  if  the  substances  introduced  as  food  were 
oxidised  exclusively  within  the  body,  the  respiratory  quotient  in  a 
pure  carbohydrate  diet  would  be  =  1,  in  a  fatty  diet  =  0-71,  in  a 
protein  diet=O78.  But  since  not  only  do  the  food-substances 
introduced  into  the  body  share  in  its  oxidative  processes,  but  the 
various  tissue-forming  substances  also  take  part,  it  seldom  happens 
that  the  respiratory  quotient  rises  to  1,  i.e.  for  the  most  part 
it  is  represented  by  a  variable  proper  fraction.  It  is  only 
under  special  circumstances  that  the  respiratory  quotient  may 
temporarily  attain  the  value  of  1,  or  even  exceed  it,  as  when  fats 
are  formed  from  carbohydrates  in  the  body,  or  when  there 
is  a  rapid  diminution  in  the  oxygen  ,content  of  inspired  air 
(Rosenthal,  1902).  An  apparent  increase  of  the  quotient  may 
appear  in  certain  birds  in  whose  crop  there  is  fermentation  of  the 
food  stored  there,  with  production  of  C02. 

It  is  a  very  interesting  fact  that  the  respiratory  quotient 
oscillates  with  the  substances  that  predominate  in  the  food :  in  a 
diet  mainly  composed  of  starch  the  value  rises  to  0'9 ;  in  a  diet 
that  is  chiefly  fatty  it  drops  to  0*55  ;  while  lastly,  in  a  diet 
mainly  consisting  of  meat  it  attains  an  intermediate  value  of 
0*7-0'65.  In  an  ordinary  mixed  diet  the  respiratory  quotient  is 
about  0-8. 

When  we  consider  the  metabolism  or  material  exchanges  of  the 
body  as  a  whole,  we  shall  examine  the  importance  of  these  and 
other  facts  relating  to  the  oscillations  of  the  respiratory  quotient ; 
we  shall  discuss  the  different  methods  employed  for  animals,  or 
man,  in  the  study  of  the  absolute  magnitude  of  the  respiratory 
gas  exchanges ;  we  shall  see  that  this  magnitude  changes  with  age, 
sex,  constitution,  external*  temperature,  work  or  rest,  the  different 
hours  of  the  day  or  night,  etc.  These  investigations  obviously 
exceed  the  limits  of  the  physiology  of  the  respiratory  apparatus,  and 
involves  the  functioning  of  the  body  as  a  whole. 


400  PHYSIOLOGY  CHAP. 


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VOL.  I  2  D 


CHAPTEE   XII 

MECHANICS   OF   RESPIRATION 

SUMMARY. — 1.  Historical.  2.  Glandular  structure  of  the  lungs.  3.  Conditions 
of  the  lungs  and  other  viscera  within  the  thorax  ;  passive  movements  due  to 
variations  in  the  negative  thoracic  pressure.  4.  The  thoracic  cavity  :  changes  of 
form  and  dimensions  with  inspiratory  and  expiratory  movements.  5.  Muscular 
mechanism  of  inspiratory  and  expiratory  movements.  6.  Normal  and  forced 
respiration.  7.  Accessory  or  concomitant  respiratory  movements.  8.  Ventilation 
or  renewal  of  pulmonary  air  (spirometry),  and  respiratory  pressure  in  the  air- 
passages  (pneumatometry).  9.  Respiratory  displacement  of  the  lungs,  and 
acoustic  phenomena  of  percussion  and  auscultation.  10.  Respiratory  variations 
of  intra-thoracic  and  intra- abdominal  pressure.  11.  Respiratory  variations  of 
pressure  in  the  vena  cava.  12.  Respiratory  variations  of  aortic  pressure. 
13.  Effect  of  respiratory  mechanics  on  the  circulation  of  the  blood.  14.  Special 
forms  of  respiratory  movements.  Bibliography. 

IN  order  that  the  respiratory  gas  exchanges  may  be  adequate  for 
the  needs  of  ordinary  life,  it  is  essential  that  the  air  contained  in 
the  alveoli  of  the  lungs  should  be  constantly  renewed.  A  slow  but 
continuous  replacement  of  alveolar  air  occurs  by  diffusion  with 
the  air  contained  in  the  respiratory  tract,  which  is,  as  we  have 
seen,  persistently  richer  in  oxygen  and  poorer  in  carbonic  acid, 
from  the  small  to  the  large  bronchi,  and  from  these  to  the  trachea. 
This  renewal  by  diffusion  is  facilitated  by  the  gentle  impacts  given 
to  the  lungs  by  the  rhythmical  movements  of  the  heart  (cardio- 
pneumatic  movements,  as  discussed  in  Chap.  VII.  10).  During  the 
physiological  lethargy  of  hibernating  animals,  and  in  the  profound 
cataleptic  state  of  apparent  death  produced  under  certain  morbid 
conditions,  or  by  hypnotic  influences,  such  as  are  employed  by  the 
Indian  fakirs,  this  occult  and  silent  renewal  of  the  pulmonary  air 
may  suffice  to  maintain  life  for  a  long  time,  since  the  physiological 
need  of  respiration  is  extraordinarily  reduced.  But  under  normal 
conditions  there  is  a  crying  want  for  more  energetic  replacement 
of  the  air  by  a  real  pulmonary  ventilation,  produced  by  the 
alternate  rhythmical  expansion  and  retraction  of  the  thorax,  in 
which  the  lungs  are  hermetically  enclosed — these  organs  being 
eminently  elastic,  and  yet  capable  of  passively  following  the 
thorax  when  it  acts  as  a  suction  and  a  pressure  pump. 

I.  The  simplest  and  most  fundamental  experiments  on   the 

402 


CHAP,  xii         MECHANICS  OF  KESPIKATION  403 

mechanics  of  respiration  are  those  of  Galen  (A.D.  131-203).  He 
was  the  first  to  assert  that  the  lungs  passively  followed  the 
movements  of  the  thorax,  but  he  assumed  that  there  was  a  layer 
of  air  between  the  pulmonary  walls  and  the  thorax. 

Oribasus  (A.D.  360)  was  the  first  who  noticed  the  collapse  of 
the  lung  in  double  pneumothorax,  and  Vesalius  (as  we  have  seen, 
p.  371)  the  first  who  employed  artificial  respiration  by  a  bellows 
inserted  into  the  opened  thorax  to  maintain  life. 

Malpighi(  1661)  first  described  the  structure  of  the  lungs.  Alfonso 
Borelli  (1679)  first  formulated  a  complete  theory  of  the  mechanism 
of  pulmonary  ventilation.  To  Haller  (1780)  belongs,  however,  the 
merit  of  explicitly  denying  that  the  pleural  cavity  contains  air — a 
notion  which  manyolung  to,  producing  not  a  little  confusion  of  ideas. 
He  further  asserted  the  absolute  passivity  of  the  movements  of 
the  lungs,  which  some  of  the  earlier  physiologists  regarded  as  the 
primum  movens  of  pulmonary  ventilation,  while  others  after  him 
(Eudolph,  1821 ;  Laennec,  1819)  still  believed,  on  the  strength  of 
fallacious  or  wrongly  interpreted  observations,  that  the  lungs 
were  capable  of  active  movements  independent  of  the  thorax. 

The  exact  determination  of  the  muscular  mechanisms  that 
govern  the  alternate  acts  of  inspiration  and  expiration,  and  the 
right  appreciation  of  their  functional  value  in  normal  (eupnoea) 
and  abnormal  (dyspnoea)  respiratory  rhythm,  is  still  the  subject  of 
innumerable  controversies,  as  we  shall  see  in  the  course  of  the 
present  chapter. 

II.  We  must  leave  the  full  description  of  the  structure  of  the 
lungs  and  air-passages,  i.e.  the  trachea,  and  the  large  and  small 
bronchi  which  lead  to  the  alveoli  (where,  as  we  have  seen,  the  gas 
exchanges  between  air  and  blood  are  carried  on),  to  text-books  of 
anatomy  and  histology ;  it  is  sufficient  here  to  remark  that  from 
the  physiological  point  of  view  they  may  be  regarded  as  large 
branching  glands  lined  with  mucosa,  in  which  the  ramified 
bronchial  tubes  represent  the  excretory  canals,  and  the  infundibuli 
divided  by  internal  septa  into  alveoli,  or  terminal  air-cells  of 
somewhat  polygonal  form,  the  secreting  glands.  These  air-cells 
are  lined  with  a  single  layer  of  cells,  which  are  characterised  by 
their  reduction  to  thin  laminae,  some  nucleated,  others  non- 
nucleated,  which  accounts  for  their  secretory  activity  being 
reduced  to  a  minimum,  as  suggested  tentatively  in  the  previous 
chapter,  or  entirely  wanting,  as  held  by  the  great  majority  of 
physiologists.  In  immediate  contact  with  the  alveolar  epithelium 
is  the  network  of  pulmonary  capillaries,  with  exceedingly  fine 
meshes,  in  the  centre  of  which  lies  the  denser  and  nucleated  part 
of  the  epithelial  cells,  while  the  more  attenuated  marginal  cells, 
which  are  reduced  to  a  delicate  lamella,  invest  the  surface  of  the 
capillaries  facing  the  alveoli,  so  that  the  capillary  network  and 
the  epithelium  which  lines  them  internally  form  but  a  single  layer. 


404  PHYSIOLOGY  CHAP. 

Each  infundibulurn  is  surrounded  by  connective  tissue,  rich  in 
elastic  fibres,  and  containing  blood  and  lymph  vessels.  A  certain 
number  of  infundibuli,  with  their  respective  bronchioles,  inter- 
connected by  connective  and  elastic  tissue,  and  by  larger 
vessels,  make  up  the  pulmonary  lobules,  provided  in  their  turn 
with  lobular  bronchi,  which  arise  from  the  junction  of  the 
bronchioles.  A  number  of  these  lobules,  united  by  the  said 
tissues,  by  still  larger  vessels,  and  by  lobar  bronchi,  form  the 
pulmonary  lobes  which  in  conjunction  make  the  lung. 

The  structure  of  the  respiratory  passages  changes  gradually 
from  bronchioles  to  lobular  bronchi,  from  these  to  the  lobar 
bronchi,  from  the  larger  bronchi  to  the  trachea.  We  must  confine 
ourselves  to  stating  that  the  bronchioles  are  lined  with  a  single 
layer  of  cubical,  non-ciliated,  epithelial  cells,  surrounded  with  a 
thin  sheath  of  connective  and  elastic  tissue,  sparsely  provided 
with  smooth  muscle  fibres.  The  epithelium  of  the  lobular  bronchi 
is  cylindrical  and  ciliated,  and  the  tube  consists  of  an  external 
sheath  of  connective  tissue,  rich  in  elastic  fibres  and  concentrically 
arranged  smooth  muscle  cells.  In  the  interlobular  'and  lobular 
bronchi  the  tube  is  more  muscular  and  somewhat  rigid,  because 
the  coat  of  elastic  and  connective  tissue,  found  on  the  outside  of 
the  circular  muscular  layer,  contains  small  irregularly  distributed 
plates  of  hyaline  cartilage.  These  cartilage  plates  become  larger 
in  the  direction  from  medium  to  greater  bronchi,  while  the 
transverse  layer  of  muscle  diminishes.  The  mucosa  thickens 
from  small  to  large  bronchi.  The  epithelium  is  stratified  (three 
or  more  layers  of  cells) ;  between  the  cylindrical  ciliated  cells 
mucous  goblet  cells  are  occasionally  visible.  Beneath  the  epithelium 
is  a  reticulated  adenoid  tissue  with  thin  elastic  fibres,  and  on  the 
outside  a  compact  and  conspicuous  elastic  layer,  formed  of  the 
predominantly  longitudinal  fibres,  which  are  arranged  in  a 
network,  in  which  are  many  small  mucoid  and  acinous  glands, 
opening  into  the  lumen  of  the  bronchus  by  small  ducts  that 
pierce  the  elastic  layer,  reticulated  tissue,  and  epithelium.  The 
mucous  secretion  of  the  goblet  cells  and  small  glands  intercepts 
the  solid  particles  introduced  with  the  air,  while  the  cilia  drive 
the  mucus  with  the  agglutinated  particles  towards  the  trachea 
and  larynx. 

The  tracheal  tube  is  much  more  rigid,  since  the  elastic  sheath 
is  more  external  and  tougher,  and  contains  rings  of  hyaline 
cartilage,  interrupted  at  the  back  and  completed  by  bundles  of 
smooth  muscle  fibres,  stretched  transversely  across  the  ends  of 
the  cartilage,  while  a  few  other  muscle  bundles  run  longitudinally 
outside  the  former.  The  tracheal  mucosa  is  not  essentially 
different  from  that  of  the  greater  bronchi,  and  contains  more 
mucous  glands.  The  strong  elastic  layer  adjusts  the  mucosa  to 
the  longitudinal  alterations  of  the  tube,  keeping  it  tense  and 


xii  MECHANICS  OF  EESPIEATION  405 

smooth.  The  smooth  muscle  cells  found  along  the  air-passages, 
and  most  abundantly  in  the  smallest  bronchi,  are  able,  according 
to  the  degree  of  their  tonus,  to  alter  the  lumen  of  the  canal  as 
required. 

III.  The  lungs  of  the  foetus  are  void  of  air  (atelectatic),  and 
therefore  sink  (in  the  test  known  as  docimasia  hydrostatica)  when 
immersed  in  water.  The  first  respiratory  movements  which 
occur  after  birth  expand  the  alveoli  of  the  lungs  and  fill  them 
with  air,  and  lungs  removed  from  any  individual  who  has  already 
breathed  float  on  the  surface  of  water  in  docimasia  hydrostatica, 
because  the  elastic  retraction  they  undergo  when  the  thorax  is 
opened  is  not  strong  enough  to  expel  all  the  air  from  the  alveoli. 
This  is  because  the  capillary  bronchi  or  bronchioles  (which,  as  we 
have  seen,  contain  no  cartilaginous  platelets  such  as  give  a  certain 
rigidity  to  the  larger  bronchi)  collapse,  and  hinder  the  complete 
expulsion  of  the  alveolar  air.  The  lungs  of  a  new-born  infant, 
which  has  already  breathed,  may  after  a  certain  time  become 
atelectatic  again  by  the  reabsorption  of  the  air  which  they  contain. 
From  the  same  cause  the  lungs  of  a  man  or  other  animal  become 
atelectatic  in  a  few  hours,  if  the  pleural  cavity  has  been  opened  on 
one  side. 

The  form  and  volume  of  the  atelectatic  foetal  lungs  correspond 
exactly  with  the  form  and  volume  of  the  thoracic  cavity  in  which 
they  are  enclosed.  They  are  in  perfect  elastic  equilibrium,  since 
on  opening  the  thorax  they  do  not  retract,  and  if  a  mercury  or 
water  manometer  is  connected  with  the  trachea  so  as  to  measure 
the  intrathoracic  pressure  (Bonders),  it  is  found  to  be  equal  to 
atmospheric  pressure,  the  manometer  showing  no  movement  on 
opening  of  the  thoracic  wall  (Bernstein). 

These  conditions  gradually  alter  during  extra-uterine  life.  As 
the  thorax  grows  more  rapidly  than  the  lungs,  these  are  thrown 
into  a  state  of  increasing  elastic  tension,  in  proportion  as  the 
difference  between  the  capacity  of  the  thorax  and  the  volume  of 
the  lungs  increases,  when  they  are  respectively  in  the  normal 
position  of  equilibrium.  This  can  easily  be  determined  by  Bonders' 
method  on  the  bodies  of  persons  of  different  ages,  provided  they 
did  not  die  of  pulmonary  diseases.  If  a  manometer  is  connected 
with  the  trachea  of  a  dead  new-born  infant,  that  had  breathed,  the 
lungs  do  not  retract,  and  the  column  of  mercury  does  not  rise,  on 
opening  both  pleural  cavities;  the  same  conditions,  therefore, 
persist  after  birth  as  in  the  foetal  atelectatic  lung  (Hermann). 
When,  on  the  contrary,  the  same  experiment  is  repeated  on  the 
body  of  an  adult,  the  lungs  retract  more  or  less  according  to  age, 
by  elastic  recoil,  till  they  are  in  equilibrium  with  a  column  of 
mercury  of  5-7*5  mm.  Accordingly,  in  the  cadaveric,  or  the 
passive  respiratory  position  of  the  adult  thorax,  it  is  the  atmo- 
spheric pressure  which  acts  within  the  pulmonary  air-passages, 

VOL.  I  2  D  a 


406  PHYSIOLOGY  CHAP. 

and  cannot  act  upon  the  surface  of  the  lungs  (these  being  her- 
metically enclosed  in  the  thoracic  cavity,  formed  mainly  of  rigid 
walls),  that  determines  the  passive  distension  as  well  as  the, 
elastic  tension  of  the  same,  and  the  negative  pressure  within  the 
thoracic  cavity  in  the  expiratory  position. 

Normally  the  thoracic  cavity  is  completely  filled  by  the  lungs, 
which  adapt  themselves  perfectly  to  its  conformation.  The  two 
layers,  visceral  and  parietal,  of  the  pleura,  are  in  immediate 
contact,  separated  only  by  the  thinnest  stratum  of  lymph,  which 
facilitates  the  gliding  of  one  over  the  other.  The  pleural  cavities 
are  potential  only :  under  morbid  conditions  they  are  formed  by 
the  liquid  or 'solid  exudation  that  is  poured  out  between  the  two 
layers  ;  or  by  a  unilateral  or  bilateral,  external  or  internal,  aperture 
in  the  same.  The  rapid  death  by  asphyxia  in  double  pneumo- 
thorax  shows  the  passivity  of  the  lung  movements,  owing  to  which 
ventilation  or  renewal  of  the  air  essential  to  the  life  of  the  animal 
ceases.  When,  however,  from  the  partial  or  complete  occlusion 
of  the  opening,  the  air  cannot  freely  enter  or  leave  the  pleura! 
cavities,  the  lungs  are  still  able  to  distend ;  this  explains  why  in 
many  cases  of  perforation  of  the  thorax  the  respiratory  gas 
exchanges  are  not  profoundly  modified. 

Besides  the  lungs,  the  thoracic  cavity  also  contains  the  heart 
with  the  large  venous  and  arterial  trunks,  which,  as  hollow  organs, 
indirectly  feel  the  effects  of  the  atmospheric  pressure  acting 
directly  upon  the  extrathoracic  vessels  that  communicate  with  the 
heart.  Intrathoracic  negative  pressure  accordingly  determines 
not  merely  the  distension  of  the  lungs,  but  also  that  of  the  heart 
and  intrathoracic  vessels,  in  proportion  with  their  capacity  for 
dilatation.  The  thick-walled  ventricles  of  the  heart,  and  the 
arteries,  which  are  always  under  strong  internal  pressure,  feel 
little  or  no  effect  from  the  negative  intrathoracic  pressure  ;  the 
auricles  and  large  trunks,  on  the  contrary,  which  have  thin  walls, 
and  are  not  distended  by  positive  internal  pressure,  suffer  a  certain 
degree  of  expansion,  by  which  the  lumen  is  widened,  and  the 
course  of  the  blood  from  the  extrathoracic  to  the  intrathoracic 
veins  facilitated. 

The  oesophagus,  as  a  hollow  intrathoracic  organ  communicating 
with  the  exterior,  should  dilate  to  a  certain  extent  in  consequence 
of  the  negative  pressure  that  obtains  within  the  thorax  ;  its  cavity, 
however,  is  potential,  and  is  only  formed  when  the  canal  is 
traversed  by  foreign  bodies,  such  as  food.  Under  ordinary  con- 
ditions the  walls  of  the  oesophagus  are  in  contact,  so  that  the 
lumen  is  obliterated,  and  the  negative  intrathoracic  pressure,  far 
from  aspirating  air  into  the  canal,  only  makes  the  walls  adhere 
more  closely,  in  consequence  of  the  atmospheric  pressure  exerted 
externally  upon  its  intrathoracic  portion.  But  if  a  hollow 
sound  is  passed  through  the  oesophagus,  it  is  converted  into 


XII 


MECHANICS  OF  KESPIEATION 


407 


an  intrathoracic  cavity  communicating  with  the  exterior,  and 
subject,  like  the  lungs,  to  all  the  changes  of  intrathoracic  pressure 
(Luciani).  The  method  of  automatic  registration  of  variations  of 
intrathoracic  pressure  by  the  oesophageal  sound,  which  we  intro- 
duced into  the  experimental  technique  of  physiology  in  1877,  is 
based  on  this  fact. 

In  conclusion  it  must  be  noted  that  the  negative  intra- 
thoracic pressure  also  affects  the  soft  movable  portions  of  the 
walls  of  the  thorax,  more  particularly  the  diaphragm,  by  which  its 
floor  is  separated  from  the  ab- 
dominal cavity  and  the  inter- 
costal spaces.  The  former,  as 
well  as  the  latter,  are  during 
the  expiratory  position  of  rest, 
and  in  the  dead  body,  curved  or 
bent  towards  the  thorax,  where 
pressure  is  negative,  while  they 
are  subjected  externally  to  at- 
mospheric pressure. 

IV.  Let  us  now  consider  the 
changes  in  form  and  dimensions 
exhibited  by  the  thorax  during 
the  alternate  movements  of  ex- 
pansion (inspiration)  and  con- 
traction  (expiration),  which 
compose  the  respiratory  rhythm. 

During  inspiration  the  whole 
thoracic  cavity  dilates  more  or 
less,  in  its  several  diameters,  in 
proportion  to  the  intensity  of 
contraction  and  the  number  of 
muscles  which  come  into  play. 

The  dilatation  of  all  the 
horizontal  diameters  of  the 
thorax  is  the  effect  of  the '  rais- 
ing of  the  ribs,  which,  with  the 
vertebral  column,  with  which 
they  articulate  posteriorly,  and  the  cartilaginous  prolongations 
and  the  sternum,  to  which  they  are  united  anteriorly,  form  the 
skeleton  or  rigid  system  of  the  thorax. 

The  ribs,  to  the  number  of  twelve  on  each  side,  constitute  a 
series  of  long,  slender,  arched  bones,  which  start  from  the  dorsal 
vertebrae  to  extend  outwards  and  forwards.  They  slant  obliquely 
from  above  downwards,  so  that  their  points  of  posterior  articulation 
are  a  little  above  the  anterior  end,  which  is  united  with  the 
sternum  by  means  of  the  cartilaginous  prolongations,  directly 
(first  seven  ribs)  and  indirectly  (eighth,  ninth,  tenth  ribs).  The 


FIG.  173.— Right  half  of  thoracic  skeleton. 
(Spaltenholtz.) 


408  PHYSIOLOGY  CHAP. 

two  last  ribs  are  loose,  and  are  of  less  importance  in  the  respiratory 
mechanism  (Fig.  173). 

By  means  of  a  double  articulation  with  two  vertebral  bodies 
and  with  a  transverse  process,  each  rib  is  able  to  rotate  round  an 
approximately  horizontal  axis,  which  passes  along  its  neck,  and 
forms  a  greater  or  lesser  angle  with  the  horizontal  plane.  The 
axes  of  rotation  of  the  two  corresponding  ribs  are  convergent  in 
front,  and  decussate,  forming  angles  that  decrease,  according  to 
Volkmann,  from  the  first  to  the  tenth  rib  (from  125°-88°).  It 
follows  that  in  the  upward  rotation  of  the  ribs,  the  point  of  the 
costal  arch  which  rises  most,  corresponds  not  with  the  anterior  end 
of  the  rib,  but  with  a  lateral  point  of  the  costal  convexity,  through 
which  passes  a  tangent  parallel  to  the  axis  of  rotation,  as  shown  in 
Fig.  174.  And  since  the  angle  formed  by  the  anterior  crossing  of 
^  Q  u ,  the  axes  of  rota- 

tion diminishes  from 
above  downwards, 
the  point  of  maxi- 
.  mal  rise'  for  the 
/  different  ribs  in  in- 
spiration is  displaced 
and  pushed  more 
towards  the  side,  in 
proportion  with  the 
descent  from  the 
first  to  the  tenth 
rib. 

FIG.  174.— Horizontal  projection  of  costal  ring  formed  by  5th  ribs.  lhe    increase    111 

(Luciani.)     ub  and  a'b'  are  the  two  axes  of  rotation  of  the  nKlinnp       fransMrarao 

double  costo- vertebral  articulation,  which  cross,   forming  in  L    imlut!>      irdllBVeise, 

this  case  an  angle  of  70°.     The  tangent  c',  parallel  to  a'b',  shows  and  anterO-pOSteriOr 

the  point  of  greatest  elevation  of  the  arch  in  inspiration.  j  .  ,r  . 

diameter  also  varies 

in  the  different  costal  hoops,  becoming  greater  in  proportion  to  the 
inclination  of  the  ribs,  and  to  their  length  and  curvature. 

With  the  rise  and  forward  inclination  of  the  ribs  the  sternum 
is  also  displaced,  describing  an  arc  of  a  circle  from  above  down- 
wards, and  from  behind  forwards,  in  the  vertical  sagittal  plane  of 
the  thorax.  Since  this  forward  and  upward  displacement  of  the 
sternum  is  least  at  its  upper,  and  greatest  at  its  lower  end,  it 
follows  that  the  different  sections  of  the  sternum  must  bend  a  little 
towards  each  other,  and  the  costal  cartilages  make  a  slight  revolution 
round  their  longitudinal  axes. 

In  consequence  of  the  inclination  of  the  ribs  and  their  elasticity, 
the  curvature  increases  when  they  rise  to  an  approximately 
horizontal  position;  on  the  other  hand,  at  the  junctions  of  their 
anterior  ends  with  the  cartilages,  the  curvature  becomes  slightly 
flattened,  which  induces  a  certain  widening  of  the  intercostal  spaces, 
proportional  to  the  degree  of  their  inclinations  and  respiratory 


XII 


MECHANICS  OF  EESPIKATION 


409 


elevation.  According  to  Ebner,  this  dilatation  is  not  perceptible  in 
the  two  first  intercostal  spaces,  owing  to  the  low  inclination  of  the 
first  ribs  and  the  minimal  rise  of  the  upper  end  of  the  sternum. 

The   inspiratory   dilatation   of  the   vertical  diameter   of  the 
thorax  is  not  directly  visible  from  without,  as   it   is    produced 
by  the  descent  of  the  diaphragm,  but  it  may  be  estimated  from 
the   rise  in  the  upper   end   of 
the  abdominal  wall,  owing   to 
the  displacement  of  the  viscera 
that  occupy  the  diaphragmatic 
concavity. 

The  inspiratory  muscular 
contractions  which  displace  the 
bones  of  the  thorax  from  the 
position  of  equilibrium  are  op- 
posed 'by  various  resistances, 
due  to  the  weight  of  the  parts 
to  be  lifted,  the  elasticity  of  the 
costo-vertebral  ligaments  of  the 
costal  cartilages  and  bones,  and 
lastly  to  the  elastic  resistance 
of  the  lungs  which  produces 
negative  intrathoracic  pressure, 
and  the  elastic  resistance  of 
the  gases  in  the  alimentary 
canal  which  work  against  the 
downward  movement  of  the 
diaphragm.  It  follows  that  when 
the  inspiratory  and  dilating 
mechanisms  of  the  thorax  cease 
to  work,  the  bones  of  the  thoracic 
cavity  return  spontaneously  to 
the  mean  position  of  equilibrium, 
either  from  gravity  or  from  the 
elastic  reaction  of  the  ligaments, 
cartilages,  ribs,  and  lungs,  as 
well  as  of  the  stomach  and  in- 
testines. We  shall,  however,  see  that  the  movements  of  expiration, 
or  retraction  of  the  thorax,  are  always  aided  by  expiratory  muscular 
contractions,  which  tend  not  only  to  bring  the  bones  of  the 
thoracic  cavity  back  into  the  position  of  equilibrium,  but  to  force 
them  beyond  this  position  by  giving  the  ribs  a  twist  from  above 
downwards,  till  in  the  forced  or  dyspnoeic  respiration  they  reach 
the  maximal  constriction  of  the  thorax  and  diminution  of  its 
several  diameters. 

V.  Of  the  inspiratory  muscles  the  diaphragm  (Fig.  175)  is  of 
the  first  importance,  owing  to  its  conspicuous  action.     By  the 


FIG.  175.— Lower  half  of  thorax  with  four  lumbar 
vertebrae.  (Luschka.)  Diaphragm  seen  from 
the  front  ;  a,  (ith  dorsal  vertebra  ;  It,  4th 
lumbar  vertebra ;  c,  ensiform  process ;  d,  d', 
aorta,  which  enters  diaphragm  by  special 
aperture  ;  e,  oesophagus  ;  /,  aperture  in  tendon 
of  diaphragm  for  passage  of  vena  cava  inferior  ; 
1,  2,  3,  trilobate  expansions  of  tendinous  centre ; 
4,  5,  costal  portions,  right  and  left,  of  dia- 
phragm muscle ;  6,  7,  right  and  left  crura  of 
diaphragm ;  8,  8,  internal  intercostal  muscles, 
which  are  absent  near  the  vertebral  column, 
where  it  joins  the  external  intercostals  ;  9,  9, 
10,  10,  subcostal  muscles  of  left  side. 


410 


PHYSIOLOGY 


CHAP. 


contraction  of  its  muscular  fibres,  which  converge  towards  the 
trilobate  tendinous  centre,  the  convexity  towards  the  thoracic 
cavity  diminishes,  pushing  the  abdominal  viscera  downwards. 
According  to  Hasse  (1880),  during  maximal  inspiration  the  right 
lobe  of  the  tendinous  centre  descends  2'5  cm.,  the  left  lobe  2  cm., 
and  the  central  lobe  about  1  cm.  The  muscle  fibres  inserted  in 
the  cartilages  of  the  six  last  ribs  contribute  to  the  elevation  and 

expansion  of  the  lower  ribs, 
since  they  are  directed  almost 
vertically  upwards,  the  vault 
of  the  diaphragm  being  sup- 
ported by  the  abdominal 
viscera  (Duchenne).  The  an- 
terior muscle  fibres,  which  run 
more  horizontally  towards 
the  tendinous  centre,  oppose 
a  certain  resistance  to  the 
forward  displacement  of  the 
sternum.  This  may  be  the 
reason  why  the  sternum  is 
bent  in  patients  who  have 
suffered  a  long  time  from 
asthma  (Thane).  Nor  is  the 
action  of  the  diaphragm  con- 
fined to  increasing  the  vertical 
diameter  of  the  thorax  with 
inspiration,  as  all  admit.  It 
also  (by  aiding  the  elevation 
and  expansion  of  the  false  ribs) 

Fin.  iW.-Deei,  and  prevortebral  muscles  of  neck.  aSSlstS    the    dilatation    of    the 

(Allen  Thomson.)    a,  Superficial  section  of  basilar  transverse  diameter  of  thebaSC 
process  ;    b,    transverse    process    of    atlas;    <•,        p ,  •,       ,  -,  j  j-r>       ,v 

transverse  process  of  7th  cervical  vertebra  ;  d,  d',  OI  the  tnorax,  and  modifies  tllG 

bodies  of  1st  and  4th  dorsal  vertebra;   e,  c',  1st  omWIifipafinTi    nf    j-V,0     aon-iffo! 

and  2nd  ribs ;  1,2,  rectus  capitis  anterior  major  amplification    OI     tne    Sagittal 

and  minor;   3,  8',  3",  median    upper  and  lower  diameter  at    the    level    of    the 
part   of   musculus  lon^us    colli ;    4,   4',  4",   >I. 

intertransversales  ;  5,  y  scalenus  anterior  and  its  lower     CllQ     01      the     Sternum, 
insertion  on  1st  rib;   6,  6'  scalenus  medius,  and       w     j  i~  •    i»  i  11 

insertion  on  2nd  rib;  V,  scalenus  posterior;  8,  effects     which     are     leSS     Well 

posterior  part  of  levator  scapulae  ;    !>,  splenius  known  an(J   are    usually  OV6r- 

looked. 

Other  inspiratory  muscles  are  the_  three i  scaleni  (Fig.  176), 
which  exert  traction  on  the  first  two  ribs,  and  Thus  elevate  and 
maintain  the  entire  thoracic  wall  (Duchenne). 

The  M.  levatores  costarurn  longi  et  breves,  twelve  on  each  side, 
are  able  from  their  insertion  in  the  immediate  vicinity  of  the 
costo-vertebral  articulations  to  produce  an  extensive  elevation 
in  the  anterior  ends  of  the  ribs  on  gentle  contraction  (Traube, 
Kosenthal).  The  inspiratory  action  of  the  M.  serratus  posticus 
superior  is  also  evident. 


XII 


MECHANICS  OF  BESPIKATION 


411 


Since  the  direction  of  the  fibres  in  the  M.  levatores  costarum 
and  the  M.  intercostales  externa  (Figs.  177  and  178)  coincide,  it 
is  natural  to  regard  these  also  as  inspiratory  muscles. 

The  function  of  the  intercostal  muscles,  external  as  well  as 
internal,  has,  however,  been  a  subject  of  endless  controversy, 
beginning  with  the  lively  polemic  between  Haller  and  Hamberger, 
and  lasting  into  our  own  day.  The  most  varying  and  opposite 
points  of  view  have  found  strong  supporters.  Setting  aside  the 
opinion  of  Galen  and  Bartholin,  who  reckoned  the  external 
ihtercostals  to  be  expiratory,  and  the  internals  inspiratory ;  and 
the  view  of  van  Helmont,  Arantius  and  others  who  denied  any 


FIG.  177.— Intercostal  muscles  of  5th  and  6tli  spaces.  (Allen  Thomson.)  A,  Side-view  ;  B,  back- 
view  ;  IV,  4th  dorsal  vertebra ;  V,  5Jbh  rib  and  cartilage ;  1,  1,  M.  levatores  costarum  longi 
et  breves ;  2,  2,  M.  intercostales  externa ;  3,  3,  M.  intercostales  interni,  as  shown  by 
removal  of  externi  in  lower  intercostal  space.  In  A  there  are  no  external  intercostals  in 
the  intercartilaginous  spaces  ;  in  B  there  are  no  internal  intercostals  near  the  vertebral 
column.  •• 

active  function  whatever  to  the  intercostal  muscles,  and  regarded 
them  merely  as  the  complement  of  the  thoracic  wall,  as  well  as  the 
opposite  view  of  Mayow,  Magendie,  Burdach,  etc.,  who  held  both 
externals  and  internals  to  be  alternately  inspiratory  and  expiratory 
in  function  ;  there  remain  four  other  aspects  of  the  question,  which 
are  defended  with  conflicting  arguments  by  distinguished  physio- 
logists, and  are  set  forth  in  modern  text-books : — 

(a)  Both  external  and  internal   intercostal   muscles   are   in- 
spiratory (Borelli,  Senac,   Boerhaave,   Winslow,   Haller,    Cuvier, 
Duchenne). 

(b)  Both  kinds  of  muscles  are  expiratory  (Vesalius,  Diemer- 
Brock,  Sabatier,  Beau  and  Maissiat,  Longet). 


412 


PHYSIOLOGY 


CHAP. 


(c)  The  external  intercostals  are  inspiratory,  the  internal  are 
expiratory,  with  the  exception  of  the  intercartilaginous  portions 
(Spigel,   Vesling,  Bayle,  and  Hamberger,  Hutchinson,  A.    Fick,, 
Martin,  and  Hartwell). 

(d)  The  intercostals  are  of  no  great  importance  in  regard  to 
the  movements  of  the  ribs ;  they  serve  rather  to  regulate  tension 


FIG.  178. — Deep  muscles  of  anterior  wall  of  thorax,  seen  from  behind.  (Allen  Thomson.)  a, 
Posterior  part  of  manubrium  sterni ;  b,  b,  clavicle ;  i-ix,  anterior  part  of  ribs  and  carti- 
lages;  1,  1',  M.  sterno-thyroidei ;  2,  2',  M.  sterno-hyoidei ;  3,  3',  M.  triangulares  sterni;  4,  4, 
upper  part  of  transverse  muscles  of  abdomen  which  meet  at  4'  4'  of  linea  alba  posterior ;  5, 
insertions  of  diaphragm  on  lower  ribs,  crossing  fascia  of  transverse  muscles ;  5'  bundles  of 
diaphragm  inserted  into  ensiform  process:;  6,  6',  intercostales  interni ;  7,  7,  7,  intercostales 
externi,  exposed  by  removal  of  interni. 

in  the  intercostal  spaces,  and  to  reinforce  them  during  inspiration, 
impeding  their  retraction  by  the  increased  negative  intrathoracic 
pressure  (Henle,  Meissner,  Brlicke,  von  Ebner,  Landois). 

Criticism  of  these  several  theories  would  necessitate  a  prolonged 
dissertation,  disproportionate  to  the  true  importance  of  the 
arguments  and  the  scope  of  this  text-book.  Here  we  can  only 
summarise  the  facts  that  appear  of  most  importance,  and  may 
determine  our  choice  among  so  many  opinions. 


xii  MECHANICS  OF  KESPIKATION  413 

It  is  incontrovertible  that  the  direction  of  the  fibres  in  the 
external  intercostals  between  two  ribs  is  identical  with  that  of  the 
levatores  costarum,  and  that  the  shortening  of  any  one  fibre  can 
only  occur,  notwithstanding  the  extension  of  the  intercostal  space, 
when  both  ribs  are  raised.  On  the  other  hand,  it  is  a  fact  that  the 
fibres  of  the  internal  interosseous  intercostals,  which  run  in  the 
opposite  direction,  can  only  shorten  when  the  intercostal  spaces 
are  reduced  by  the  lowering  of  the  ribs.  The  tenability  of  this 
view  is  apparent  if  we  expose  the  intercostal  muscles  of  the  thorax 
of  a  dead  body,  and  imitate  the  inspiratory  process,  by  drawing  the 
sternum  upwards  with  a  hook,  introduced  through  a  hole  in  the 
maiiubrium.  It  will  then  be  seen  that  as  the  intercostal  spaces 
widen,  the  external  intercostal  muscles  relax,  and  the  internal 
interosseous  intercostals  contract ;  this  shows  that  during  life  the 
insertions  of  the  external  intercostals  come  together  during 
inspiration,  and  those  of  the  internal  in- 
tercostals separate. 

Since  the  muscles  shorten  actively 
during  their  contraction,  and  are  passively 
elongated  by  the  action  of  the  antagonists, 
it  follows  that  the  external  intercostals 
must  be  inspiratory  and  the  internal  inter- 
costals expiratory.  Hamberger's  schema 
and  machine  (1751),  however  imperfect 
and  inadequate  as  an  exact  reproduction 

Of  the  physiological  prOCeSS,  Still  Serves  to    FIG.   179.  -  Hamberger's    schema 

olnm'rlaf-e»    f"hp  rnonTrim'nc:  of    tVn'c  fanf   fTTirr  to   demonstrate  the  functional 

ICiaate    tne  mecnaniCb  OI    tniS  laCt  (±  Ig.          antagonism  of  internal  and  ex- 

1*79).     When  the  ribs  ac  and  Id  pass  into       ternal  intercostals  (reproduced 

,       '.  .  .    .  i     T*     j.i  from  Fig.  -2  of  his  dissertation). 

the  inspiratory  position   ag  and   67,   the 

intercostal  space  dilates  (bh<ab) ;  the  sternum  gf  moves  away 
from  the  vertebral  column  al  (bfj>be);  the  fibres  of  the  external 
intercostals  ak  shorten  (ak>al),  and  those  of  the  internal  inter- 
costals ck  lengthen  (ck<lg).  The  reverse  occurs  when  the  system 
passes  from  the  inspiratory  position  a  b  g  f  to  the  expiratory 
position  abed. 

In  regard  to  the  inspiratory  function  of  the  intercartilaginous 
muscles  which  form  the  anterior  prolongation  of  the  internal 
intercostals,  Hamberger's  explanation  is  less  convincing,  but  it  is 
intelligible  by  the  help  of  the  following  schema  (Fig.  180).  When 
the  ribs  are  curved,  they  may  be  regarded  as  rods  bent  at  an 
angle  acd  and  bef,  in  which  the  articular  points  c  and  e  represent 
the  symphysis  between  the  bony  and  cartilaginous  parts  on  which 
the  traction  is  exerted.  During  inspiration  the  fibres  of  the  inter- 
cartilaginous  muscles,  which  have  the  direction  gli,  move  the 
sternum  df  away  from  the  vertebral  column  ab,  like  the  fibres  of 
the  external  intercostals,  which  run  in  the  direction  kl.  During 
this,  double  action  the  angles  c  and  e  must  get  blunted,  because  the 


414 


PHYSIOLOGY 


CHAP. 


muscles  of  the  upper  intercostal  spaces  work  simultaneously,  and 
the  entire  thorax  is  slightly  elevated  by  the  contraction  of  the 
scaleni.  It  follows  that  both  the  external  intercostals  and  the, 
intercartilaginous  muscles  are  active  in  the  inspiratory  position, 
although  they  have  an  opposite  course  (gli^g'h',  kl>k'l').  This 
view  of  Hamberger's  was  better  illustrated  at  a  later  time  by 
Hutchinson  (1852). 

It  is  supported  as  regards  the  inspiratory  action  of  the  external 
intercostals  by  direct  observations  on  the  living.  These  muscles 
have  been  observed  on  animals  to  become  tense,  and  to  harden  and 
thicken  during  inspiration,  while  during  expiration  they  relax  and 
flatten  (Antonio  Marcacci,  1843  ;  Duchenne,  1866  ;  Kosenthal, 

1882).  When  in  the  dog 
or  cat  a  section  of  the  in- 
ternal intercostal  muscle  is 
exposed  by  care  fully  cut  ting 
away  the  external  intercostal 
that  covers  it,  so  that  both 
intercostal  muscles,  the  ex- 
ternal and  internal  of  one 
or  two  adjacent  intercostal 
spaces,  can  be  simultane- 
ously observed,  an  alternate 
contraction  of  their  fibres 
can  be  detected  —  those  of 
the  external  intercostals 
being  active  during  in- 
spiration, and  those  of  the 
internal  intercostals  during 
expiration  (Ant.  Marcacci). 

A  f    Q     lofpv    fimo     tViia     -0700 
^-l    a    «tM=r     timi  Wd8 


FIG.   180.  —  Schema  to  demonstrate  that  the  function 
of    the   internal    intercartilaginous    intercostals    is 
identical  with   that   of   the    external  interosseous    confirmed  bv  trrapllic  records, 
intercostals.  .  111  i 

which  showed  that  the 

internal  interosseal  intercostals  contract  alternately  with  the 
diaphragm,  and  therefore  have  an  expiratory  action  (Newell-Martin 
and  Hartwell,  1879). 

The  experiments  with  localised  electrical  stimulation,  which 
proved  to  Duchenne  and  others  that  there  was  always  a  narrowing 
of  the  intercostal  space  and  elevation  of  the  lower  above  the  upper 
rib,  either  when  the  external  intercostals  alone  are  stimulated,  or 
when  the  internal  are  excited  as  well,  does  not  contradict  the 
above  facts,  since  normally,  in  inspiration,  all  the  external  inter- 
costals contract  synergically,  the  thorax  being  lifted  and  supported 
by  the  scaleni,  which  must  necessarily  cause  distension  of  the 
intercostal  spaces. 

The  function  of  the  intercartilaginous  muscles,  again,  has  been 
experimentally  confirmed.  K.  du  Bois-Eeymond  and  P.  Masoin 


XII 


MECHANICS  OF  EESPIEATION 


415 


found  in  dogs,  cats,  and  rabbits  that  with  forced  respiration 
the  intercartilaginous  muscles  contract  synchronously  with  the 
diaphragm,  i.e.  are  inspiratory,  which  was  confirmed  later  on  by 
Bergendall  and  Bergmann.  E,  Fick 
(1897)  made  an  exhaustive  in- 
vestigation of  the  subject,  both 
critically  and  by  means  of  vivi- 
sections on  dogs,  and  came  to  the 
same  conclusion. 

Besides  the  internal  interos- 
seous  intercostals,  all  the  muscles 
contained  in  the  depth  of  the  ab- 
dominal wall  act  as  inspiratory  by  , 
compressing  the  abdominal  viscera, 
thus  pushing  the  diaphragm  up- 
wards and  the  lower  ribs  down- 
wards. Such  are  the  rectal 
abdominal,  the  oblique  external 
and  internal,  and  also  the  trans-  ^ 

verse  muscles.  »  ^ 

The  instruments  used  in  measuring 
the  different  diameters   of  the  thorax,    FlG-   18L  ~ 
and  the  variations  which  these  undergo 


J 


during  normal  and    forced    respiration, 
are   known   as    thoracometers.      That  of 


Sibson,  represented  in   Fig.   181,  is  the 

generally   used,    and    i 
apply. 


most   generally   used,    and    is    easy    to 


metal  rods  at  a  right  angle,  D  is  applied 
to  vertebral  column,  and  B  (which  runs 
along  the  graduated  scale  C)  carries  at 
its  extremity  a  toothed  rod  A,  provided 
with-  a  button  to  be  applied  to  the 
sternum.  This  moves  an  index,  which 
shows  the  excursions,  magnified  on  a 
dial. 


If  this  instrument  is  reduced  to  the  form  of  a  measuring  compass 
(callipers),  the  limb  A,  which  runs  in  a  cogged  wheel,  and  moves  the 
indicator  of  the  dial,  being  replaced  by  a  capsule  covered  with  a  rubber 
membrane,  kept  taut  by  an  elastic  spring,  and  provided  with  a  button,  the 


FIG.  182. — Marey's  Pneumograph  (latest  model).  Flexible  steel  plate,  curved  by  the  traction  of 
two  arms  of  a  lever  joined  at  the  circumference  of  the  thorax  by  a  silk  band.  The  curve  of  the 
plate  is  shown  by  a  lever  attached  to  the  centre  of  the  elastic  membrane  of  an  exploring 
tambour.  This  records  the  pneumogram  inversely  upon  a  revolving  drum,  i.e.  the  descending 
line  corresponds  with  the  inspiratory  dilatation  of  the  thorax,  and  the  ascending  line  with 
its  expiratory  retraction. 

respiratory  variations  of  any  given  thoracic  diameter  can  be  registered  on  a 
revolving  cylinder. 

This  is  the  model  on  which  the  thoracograph  of  Bert  and  of  Fick,  and 
the  stethograph  of  Burdon-Sanderson  are  constructed. 

Marey's  pneumograph  (Fig.  182),  of  which  there  are  various  types,  make& 


416 


PHYSIOLOGY 


CHAP. 


regular  and  measurable  tracings  of  the  variations  of  the  thoracic  circum- 
ference.    It  is  one  of  the  instruments  most  employed  for  clinical  purposes. 

Eosenthal's  phrenograph  is  used  to  obtain  exact  tracings  of  the  excursions 
of  the  diaphragm.  It  consists  in  a  spatula-shaped  lever,  applied,  aftef/ 
making  an  opening  in  the  median  line  of  the  epigastrium,  to  the  concave 
vault  of  the  diaphragm.  A  simpler  method  is  that  which  introduces  a  flat 
elastic  rubber  bag  between  the  diaphragm  and  the  abdominal  organs,  which 
is:  compressed  when  the  diaphragm  contracts,  and  decompressed  on  its 
relaxation,  these  effects  being  transmitted  to  a  Marey's  writing  tympanum 
(Foster).  This  method  records  not  only  the  movements  of  the  diaphragm, 

but  also  the  alternate  contrac- 
tions of  the  abdominal  muscles. 
The  simplest  method,  which 
involves  110  vivisection,  and  is 
therefore  applicable  to  man, 
consists  in  applying  the  button 
of  an  exploring  tympanum, 
or  of  Vierordt's  sphygmo- 
graph,  or  of  Burdon-Sander- 
son's  cardiograph  (Fig.  107, 
p.  267)  to  any  point  of  the 
epigastrium.  In  man  (who, 
as  we  shall  see,  breathes  with- 
out active  intervention  of  the 
abdominal  muscles)  this 
method  yields  fairly  satis- 
factory results. 

VI.  After  defining  the 
inspiratory  and  expiratory 
muscular  mechanisms,  on 
which  depend  the  rhyth- 
mical expansion  and 
contraction  of  the  thor- 
acic cavity,  we  next  have 
to  determine  which  of 
these  intervene  and  have 
a  preponderating  action 
during  normal  respiration, 

FIG.   183.  —  Diagram    of    variations   of    antero  -  posterior    an(J  wnicn  come  HltO 


TV' 


. 

diameter  of  thorax  and  abdomen  in   the  two  sexes 
during    normal    breathing   and    forced    respiration,    m      lorCCd      Or 

respiratory  rhythm. 

Even  in  ordinary  quiet  breathing  two  types  of  respiratory 
movements  can  be  distinguished,  the  abdominal  and  the  costal  ; 
in  the  former  the  activity  of  the  diaphragm  is  the  more  pro- 
nounced, in  the  latter  that  of  the  external  in  tercostals,  or  generally 
speaking,  of  the  muscles  by  which  the  ribs  are  elevated. 

According  to  Hutchinson's  observations  (1852),  a  man's 
breathing  is  always  abdominal,  a  woman's  costal.  By  drawing  on 
a  flat  plane  the  outline  of  the  shadows  projected  by  two  persons 
of  different  sex,  at  the  several  moments  of  normal  or  forced 
respiratory  movements,  he  obtained  the  diagrams  of  Fig.  183, 
which  illustrate  very  effectively  the  two  types  of  respiration. 


xii  MECHANICS  OF  KESPIKATION  417 

During  inspiration  and  quiet  expiration,  the  anterior  profile  of  the 
thorax  and  abdomen  oscillate  between  the  limits  of  the  boundaries 
of  the  black  line  nn '.  It  will  be  seen  that  this  tract  is  deepest  in 
man  at  the  level  of  the  epigastrium,  and  in  woman  at  the  upper 
region  of  the  mammae.  The  excursion  of  the  thoracic-abdominal 
profile  of  maximal  inspiration  reaches  the  dotted  line  in  the  two 
figures,  and  in  maximal  expiration  it  falls  to  the  outline  of  the 
same.  It  will  be  seen  that  during  forced  respiration  there  is  no 
longer  the  marked  difference  observed  in  quiet  breathing,  between 
the  variations  of  the  sagittal  diameter  of  the  thorax  in  man  and 
woman.  In  both  there  is  maximal  costal  dilatation  and  forward 
displacement  of  the  sternum  during  forced  inspiration,  and 
maximal  abdominal  retraction  in  forced  expiration. 

According  to  Hutchinson,  the  difference  between  the  normal 
types  of  respiration  in  man  and  woman  is  not  the  effect  of  staysr 
because  this  type  of  breathing  is  seen  in  girls  who  have  never 
worn  them.  Apparently  it  is  a  secondary  sexual  character,  formed 
in  the  course  of  phylogenesis  as  the  effect  of  pregnancy,  which 
necessarily  develops  costal  respiration,  increasing  intra-abdommal 
pressure,  and  confining  the  action  of  the  diaphragm.  Many, 
however,  hold  that  the  thoracic  type  of  respiration  is  an  effect  of 
the  corset  or  ceiriture  (Beau  and  Maissiat,  Walsche,  Sibson),  and 
A.  D.  Waller  has  put  forward  the  same  opinion,  adducing  the  fact 
that  women  of  savage  races,  like  the  males,  exhibit  abdominal 
respiration. 

As  regards  the  abdominal  type  of  respiration  in  the  male  sex, 
it  is  desirable  to  correct  an  .error  that  is  widespread  even  in 
modern  text -books,  to  the  effect  that  the  diaphragm  exerts  a 
preponderating  influence  over  all  the  other  inspiratory  muscles. 
A.  Fick  (1866)  remarked  that  inspiratory  movements  can  be  pro- 
duced on  oneself,  with  a  little  practice,  by  throwing  the  diaphragm 
only  into  action.  This  is  most  easily  effected  by  associating  the 
idea  of  pressing  the  contents  of  the  abdomen  with  the  act  of 
inspiration.  During  this  purely  diaphragmatic  inspiration,  the 
transverse  and  antero-posterior  diameters  of  the  thorax  undergo 
hardly  any  change,  save  near  the  base,  where  they  are  slightly 
enlarged,  although  less  than  in  normal  costal  breathing. 
Fick  affirms  that  only  the  sagittal  diameter  near  the  ensiform 
process  increases,  and  that  the  transverse  diameter  near  the  last 
ribs  diminishes ;  but  we  have  been  unable  on  ourselves  to  verify 
this  last  assertion.  We  have  always  found  that  pure  diaphragmatic 
breathing  is  far  more  fatiguing  than  normal  respiration,  the  proof 
being  that  man  as  well  as  woman  normally  breathes  more  with 
the  whole  of  the  external  intercostal  muscles,  which  elevate  and 
extend  the  ribs,  than  with  the  diaphragm. 

If  we  assume  with  Donders  that  the  external  surface  of  the 
thoracic  cavity  covers  some  20  dcm.,  and  that  this  surface  on  an 

VOL.  i  2  E 


418 


PHYSIOLOGY 


CHAP. 


average  increases  only  some  2-5  mm.  on  every  side  by  the  action 
of  the  external  intercostals,  this  still,  according  to  Fick,  yields  a 
volume  increase  of  500  c.c.,  which  corresponds  to  the  average 
volume  of  normally  inspired  air.  According,  therefore,  to  Tick's 
calculations,  the  diaphragm  hardly  takes  any  part  in  normal 
inspiration,  or  at  most  the  tonicity  of  its  fibres  is  augmented, 
in  order  to  check  any  upward  aspiration  during  the  widening  of 
the  thorax. 

This  theory  is  evidently  exaggerated,  and  does  not  harmonise 
with  the  fact  that  in  the  quiet  breathing  of  man  the  maximal 
excursion  of  the  sagittal  diameter  is  observed  to  correspond  with 
the  epigastrium  (Fig.  183),  which  can  only  result  from  the 
inspiratory  activity  of  the  diaphragm.  The  fact,  however,  remains 


Fie.  1S4. — Thoracic  and  abdominal  pneumograms  during  waking  (T  and  A)  and  sleep  (T'  A')- 
(A.  Mosso.)  The  curves  are  reversed,  T  and  T'  being  traced  with  Marty's  pneumograph,  A  A' 
with  Vierordt's  sphygrnographic  lever  applied  near  the  umbilicus. 

that  the  function  of  the  diaphragm  is  normally  far  less  im- 
portant than  that  of  the  external  intercostals  taken  as  a  whole. 
Hultkrantz  has  recently  shown  that  in  an  individual  who 
takes  in  on  an  average  490  c.c.  of  air,  320  c.c.  are  to  be  referred 
to  thoracic  dilatation,  and  only  170  c.c.  to  the  depression  of  the 
diaphragm. 

Again,  it  appears  from  certain  curves  of  thoracic  and  abdominal 
respiration  which  Mosso  recorded  simultaneously  in  the  waking 
and  the  sleeping  states,  that  the  characteristic  abdominal  type  of 
human  respiration  in  the  waking  state  disappears  in  sleep,  during 
which  the  activity  of  the  intercostals  increases,  while  that  of  the 
diaphragm  is  reduced  to  a  minimum  (Fig.  184). 

As  regards  the  question  whether  during  normal  quiet  breathing 
the  external  intercostals  only  corne  into  play  by  the  raising  of  the 
ribs,  or  whether  the  scaleni  and  levatores  costarum  breves  et  longi 


xii  MECHANICS  OF  KESPIKATION  419 

are  also  involved,  opinions  are  much  divided,  and  no  positive  facts 
can  be  adduced  on  either  side. 

On  the  other  hand,  it  is  clear  that  in  forced  respiration  the 
action  of  all  these  muscles  is  reinforced  by  that  of  other  accessory 
muscles,  whose  ordinary  office  is  not  to  assist  the  dilatation  of  the 
thorax.  Such  are  the  sterno-cleido-mastoid,  the  pectoralis  major 
and  minor,  the  trapezius,  serratus  and  extensors  of  the  vertebral 
column.  Further,  those  muscles  intervene  actively  which  serve  to 
lower  the  larynx  and  widen  the  glottis,  as  well  as  the  muscles  of 
the  palate,  fauces,  and  dilators  of  the  nostrils. 

Another  question  which  is  difficult  to  solve,  and  as  to  which 
opinions  are  divided,  is  whether  in  normal  quiet  breathing  expira- 
tion takes  place  passively  by  simple  elastic  reaction,  or  is  actively 
promoted  by  the  interosseous  portion  of  the  internal  intercostals, 
triangularis  sterni,  and  serratus  posticus  inferior.  The  great 
majority  of  writers,  headed  by  Donders,  adopt  the  first  view ; 
Fick's  arguments  in  favour  of  the  second  seem  to  us,  however,  to 
carry  a  certain  weight.  He  showed  that  with  a  little  practice, 
active  expiration  can  be  performed  voluntarily  without  throwing 
the  abdominal  muscles  into  any  kind  of  tension.  This  is  easy  by 
concentrating  the  attention  in  expiration  on  dropping  the  upper 
ribs  and  shoulders,  and  not  breathing  the  air  out  forcibly,  which 
would  throw  the  abdominal  muscles  into  contraction.  If  during 
this  intentionally  thoracic  expiration  a  water  manometer  is 
connected  with  the  oral  cavity,  the  meniscus  can  be  seen  to  rise 
4-5  cm.,  which  gives  a  clear  idea  of  the  force  exerted  by  the 
thoracic  muscles,  and,  according  to  Fick,  proves  the  expiratory 
action  of  the  internal  intercostals,  as  to  which  there  has  been  so 
much  discussion.  That  these  do  take  part  even  in  normal 
respiratory  rhythm  is  shown  by  the  fact  that  the  expiratory  act 
can  be  voluntarily  interrupted  at  any  moment,  which  certainly 
depends  on  voluntary  inhibition  of  the  expiratory  muscles  already 
in  action,  and  not  upon  the  entry  of  the  antagonistic  inspiratory 
muscles,  about  which  we  know  very  little. 

Another  cogent  argument  in  favour  of  this  theory  seems  to  us 
to  lie  in  the  tracings  of  normal  human  respiration,  recorded  by 
Marey's  pneumograph  (Fig.  185).  Neither  the  inspiratory  nor 
the  expiratory  excursions  constantly  reach  the  same  abscissae,  as 
though  drawn  between  two  parallel  lines ;  but  they  are  now 
more,  now  less,  extensive,  according  as  in  the  different  breathings 
the  contraction  of  the  antagonistic  muscles  in  individual  respira- 
tions was  more  or  less  intense. 

To  this  it  may  be  added  that  in  dogs  (Luciani,  1877)  expiration 
under  normal  conditions  is  always  active,  owing  to  the  intervention 
of  the  abdominal  muscles,  the  contraction  of  which  normally 
prevails  over  the  alternating  contractions  of  the  diaphragm, 
in  relation  to  intra-abdominal  pressure,  which,  as  we  shall  see, 


420  PHYSIOLOGY  CHAP. 

rises  during  expiration  and  sinks  during  inspiration.  This  fact 
increases  the  probability  that  in  man  also  the  normal  expiratory 
movements  are  active,  even  if  this  be  due  to  participation  of  the 
internal  intercostals,  and  not  of  the  abdominal  muscles. 

The  most  convincing  evidence  for  the  active  character  of 
expiration  under  normal  conditions  also  was,  however,  furnished 
by  Aducco  (1887).  From  a  series  of  ingenious  experiments  per- 
formed on  men  and  dogs,  he  adduced  the  following  facts,  which 
show  as  a  whole  that  in  the  expiratory  process  the  contraction  of 
certain  muscles  co-operates  with  the  elastic  reaction  of  the  lungs, 
thorax,  abdominal  walls,  and*  intestinal  gases  : — 

(a)  Normal  expiration,  being  favoured  by  many  passive  factors, 
has  in  the  waking  state  a  longer  duration  than  inspiration,  which 
meets  with  corresponding  resistance  from  these  same  factors. 

(6)  Expiration  proceeds  quite  regularly,  even  when  some  of  its 
principal  passive  factors  are  excluded,  e.y.  after  the  abdominal  and 


FIG.  18o. — Pneumograms  taken  with  Marey's  jkneumograph  during  normal,  quiet  breathing. 
The  lower  abscissa  is  at  the  level  of  the  dead  point  of  the  deepest  inspirations  ;  the  higher 
abscissa  at  the  dead  point  of  the  more  active  expirations. 

thoracic  cavities  have  been  widely  opened  to  exclude  the  elastic 
reaction  of  the  intestinal  gases  and  distended  lungs. 

(c)  When  to  the  passive  factors  of  expiration  is  added  a  force 
which  works  in  the  same  direction  (a  rubber  sheath  compressing 
the  thorax,  a  weight  placed  on  the  thorax),  the  time  relations 
between  the  two  acts  of  respiration  is  very  little  altered. 

(d}  With  artificial  expiration  on  the  dead  body,  when  only 
passive  factors  can  come  into  play,  a  given  weight  is  invariably 
less  displaced  by  the  thoracic  walls  than  in  normal  expiration. 

(e)  Given  two  expirations  of  equal  strength,  one  made  by  the 
living  animal,  the  other  artificially  induced  on  a  dead  body  of  the 
same,  the  positive  tracheal  pressure  developed  by  the  latter  is 
lower. 

(/)  If  during  sleep,  thoracic  and  abdominal  pneumograms  are 
taken  on  a  person  breathing  through  Miiller's  water-valves,  and 
the  pressure  raised  in  the  expiratory  valve  by  adding  a  little  water, 
the  curve  (Fig.  186)  shows  that  while  thoracic  expiration  undergoes 


xii  MECHANICS  OF  RESPIRATION  421 

little  change  in  its  course  and  duration,  abdominal  respiration 
becomes  slower  in  the  middle  of  its  period.  This  slowing  is  the 
proof  that  in  quiet  breathing  the  abdominal  muscles  do  not  in  any 
way  function  as  expiratory  factors.  On  the  other  hand,  the 
absence  of  any  effects  of  increased  expiratory  resistance  in  the 
pneumograms  of  the  thorax  proves  that  the  thoracic  expiratory 
muscles  come  actively  into  play,  so  that  they  readily  overcome 
this  resistance.  Thus,  then,  "  thoracic  expiration,  even  when 
accomplished  under  conditions  of  perfect  rest,  as  is  the  case  in 
sleep,  is  an  active  process." 

VII.  The  respiratory  movements,  of  which  we  have  so  far 
treated,  directly  determine  the  alternate  filling  and  emptying 
with  air  of  the  lungs — inspiration  and  expiration.  Besides  these 
respiratory  movements  in  the  strict  sense  of  the  word,  there  are 
others,  which  affect  the  air-passages  beyond  the  bronchial  tubes  and 
the  thorax,  and  indirectly  favour  pulmonary  ventilation.  These 


FIG.  180. — Thoracic  and  abdominal  pneumograms  recorded  (with  two  exploring  button  tam- 
bours) during  quiet  sleep  of  an  individual  breathing  with  a  mask  through  Miiller's  water- 
valve.  (Aducco.)  At  T  and  A,  the  inspiratory  and  expiratory  valves  offer  least  resistance1. 
At  T'  and  A'  the  expiratory  valve  offers  higher  resistance  owing  to  addition  of  a  little  water. 
The  effect  of  this  greater  resistance  is  seen  in  the  descending  expiratory  line  of  the  abdominal 
tracing. 

are  known  as  accessory  or  concomitant  respiratory  movements. 
Some  of  them  are  purely  passive  in  character,  i.e.  they  represent 
simple  secondary  effects  of  the  respiratory  movements  proper: 
such  are  the  movements  of  the  larynx  and  trachea,  which  in 
inspiration  are  drawn  down  by  the  expansion  of  the  lungs  and  fall 
of  the  diaphragm,  rising  again  with  the  succeeding  expiration. 
Others,  however,  and  it  is  these  which  must  now  be  mentioned 
briefly,  are  of  an  active  character,  due  to  the  contraction  of  certain 
special  muscles. 

In  the  first  place,  we  must  consider  the  respiratory  movements 
of  the  laryngeal  muscles  proper,  which  produce  inspiratory  dilata- 
tion and  expiratory  constriction  of  the  glottis.  On  some  animals, 
particularly  dogs,  these  movements  may  be  regularly  observed, 
while  in  men  their  presence  in  quiet  breathing  is  much  disputed, 
since  there  seems  rather  to  be  a  permanent  widening  of  the  glottis. 
In  a  certain  percentage  of  cases  (16  per  cent,  according  to  Semon) 
these  movements  are,  however,  perceptible  in  man  during  quiet 
breathing. 


422 


PHYSIOLOGY 


CHAP. 


Next  to  the  respiratory  movements  of  the  vocal  cords  come 
those  of  the  nostrils,  which  are  essentially  analogous  with  the 
first,  and  also  appear  regularly  in  man,  in  a  certain  number  of> 
cases,  while  in  some  animals  (e.g.  rabbit)  they  are  never  wanting,, 
and  in  others  (e.g.  the  horse)  they  play  a  very  important  part, 
paralysis  of  the  corresponding  muscles  being  apt  to  produce 
suffocation.  They  consist  in  the  expansion  of  the  nostrils, 
coincident  with  inspiration  (or  more  accurately,  commencing  just 
before  the  phase  of  inspiration  proper),  and  a  subsequent  constric- 


FIG.  1ST. — Apparatus  for  registering  respiratory  movements  of  an  animal  by  the  oscillations  of 
pressure  in  the  respiratory  passages.  .S,  Hutchinson's  spirometer,  to  which  is  attached  a 
small  metal  pointer  d  which  records  the  oscillations  of  pressure  in  the  animal's  trachea 
upon  the  smoked  drum ;  R,  large  receiver  from  which  the  animal  breathes,  connected  by 
ft  to  spirometer,  by  h  to  the  trachea.  The  tube  c  permits  more  or  less  rapid  renewal  of  air 
in  receiver,  according  as  the  lumen  is  mere  or  less  constricted. 

tion,  which  coincides  more  or  less  exactly  with  the  expiratory 
phase. 

In  forced  respiration  (dyspnoea)  these  concomitant  respiratory 
movements  occur,  as  we  have  seen,  to  an  exaggerated  degree,  even 
in  individuals  in  whom  they  are  not  observed  in  normal  quiet 
respiration.  Other  movements  are  then  associated  with  them,  e.g. 
foaming  at  the  mouth,  protrusion  of  the  tongue,  etc.,  etc.,  showing 
that  the  object  is  to  give  free  access  of  air  to  the  respiratory 
passages. 

VIII.  Ventilation  or  the  renewal  of  the  pulmonary  air,  effected 
by  the  alternate  movements  of  dilatation  and  contraction  of  the 
thorax,  varies  in  proportion  to  the  varying  intensity  of  these  move- 
ments. The  name  of  tidal  air  is  given  to  the  volume  of  air  which 


xii  MECHANICS  OF  KESPIRATION  423 

enters  and  leaves  the  pulmonary  air -passages  during  a  normal 
inspiration  and  expiration.  It  can  be  measured  by  a  well- 
calibrated  and  graduated  glass  bell,  which  Hutchinson  (1860) 
termed  a  spirometer  (Fig.  187).  A  properly  constructed  gasometer, 
which  offers  minimal  resistance  to  the  passage  of  the  air,  can 
be  substituted  (Mosso). 

The  amount  of  tidal  air  varies,  according  to  Yierordt,  between 
367  and  699  c.c.  in  an  adult.  The  average  generally  taken 
is.  500  c.c.  With  an  average  frequency  of  16  respirations  per 
minute,  the  amplitude  of  pulmonary  ventilation  (Rosenthal's 
respiratory  capacity)  amounts  therefore  to  8000  c.c.  This 
amount  increases  in  proportion  as  the  respirations  are  more 
intense  and  deeper.  Hutchinson  gave  the  name  of  complementary 
air  to  that  amount  which,  after  a  normal  respiration,  may  still  be 
breathed  in  by  a  maximal  inspiration  :  of  reserve  air  to  that 
which  may  be  expelled  after  a  normal  expiration  by  a  maximal 
expiration  ;  and,  lastly,  he  termed  the  sum  of  tidal,  complement- 
ary, and  reserve  air  obtained  on  following  a  maximal  inspira- 
tion by  a  maximal  expiration,  the  vital  capacity.  The  values  of 
the  determinations  (by  means  of  spirometers)  of  the  volumes  of 
these  different  measures  of  air,  vary  considerably  in  experiments 
undertaken  on  different  individuals.  According  to  Haeser's  obser- 
vations, the  mean  vital  capacity  of  Germans  is  3222  c.c. ;  of  English 
(who  are  taller  on  an  average;,  3772  c.c.  The  vital  capacity  is 
affected  not  only  by  stature,  but  also  'by  volume  of  trunk,  body, 
weight,  age,  sex,  profession  or  trade,  condition  of  digestion  or 
inanition,  etc. 

In  order  to  avoid  a  gross  error  in  spirometry,  it  is  necessary,  as  v.  Hoesslin 
pointed  out,  to  breathe  into  a  receiver  warmed  to  body  temperature  (by 
heating  the  bottom  or  walls  of  the  spirometer,  or  filling  it  with  warm  water). 
Thus  with  a  spirometer  warmed  to  37°  C.  the  vital  capacity  amounted  to 
2850  c.c.,  while  with  the  spirometer  at  6°  C.  it  was  only  2375  c.c.,  a  difference 
of  16'5  per  cent. 

The  air  left  in  the  lungs  after  a  maximal  expiration  is  termed 
the  residual  air.  It  can  be  determined  on  the  living  by  the 
methods  of  H.  Davy  and  Grehant,  which  consist,  after  making  a 
maximal  expiration,  in  breathing  for  a  certain  time  from  a  rubber 
balloon  containing  a  known  quantity  of  hydrogen.  When  it  is 
supposed  that  all  the  residual  air  has  mixed  with  the  hydrogen, 
the  percentage  analysis  of  the  air  in  the  balloon  is  taken,  and  the 
value  of  the  residual  air  is  then  found  by  an  easy  calculation. 
In  different  experiments  these  observers  found  it  to  be  1230- 
1640  c.c.  On  an  average  it  can  be  assumed  that  the  residual  air  is 
equal  to  half  the  vital  capacity  (Gad). 

It  appears  from  the  total  of  spirometric  observations  that  in 
each  normal  respiratory  cycle  or  revolution  only  a  portion  of  the 


424  PHYSIOLOGY  CHAP. 

air  in  the  lungs  can  be  renewed,  which  part  may  be  taken  as 
•corresponding  to  J-l. 

If  in  the  course  of  a  series  of  normal  quiet  breathings  a  single 
inspiration  of  hydrogen  is  made,  and  a  sample  of  the  air  collected 
from  each  succeeding  expiration,  to  ascertain  which  no  longer 
contains  any  trace  of  hydrogen,  the  result  is,  approximately,  that 
after  6-8  cycles  the  whole  air  of  the  lungs  is  renewed;  after 
that  time  every  trace  of  hydrogen  in  the  expired  air  vanishes 
(Grehant). 

During  the  entrance  of  air  into  the  lungs  the  pressure  in  the 
air-passages  becomes  negative ;  the  pressure  during  the  exit  of  air 
from  the  lungs,  on  the  contrary,  is  positive.  In  order  to  estimate 
these  variations  of  intrapulmonary  pressure  it  is  only  necessary 
to  connect  a  mercury  manometer  with  one  nostril,  while  the 
mouth  is  kept  closed,  and  to  breathe  with  the  other  nostril 
(Bonders).  It  will  be  seen  that  in  quiet  breathing  the  mercury 
column  falls  1  mm.  during  inspiration  and  rises  2-3  mm.  in 
expiration.  These  oscillations  are  increased  in  forced  respiration. 

To  ascertain  the  maximal  values  of  negative  and  positive 
intrapulmonary  pressure,  obtained  by  exerting  all  available  in- 
spiratory  and  expiratory  forces,  it  is  only  necessary,  starting  from 
zero  pressure,  to  close  the  mouth  and  the  open  nostril,  and  then  to 
make  the  maximal  inspiratory  or  expiratory  effort.  According  to 
Bonders,  the  maximal  negative  inspiratory  pressure  is  on  an 
average  =  -  57  mm.  Hg  (36-74)  and  the  maximal  positive  expira- 
tory pressure  =  +  87  mm.  Hg  (82-100). 

When  we  consider  that  on  the  one  hand  the  iuspiratory 
muscles  have  to  overcome  great  resistances  in  order  to  dilate  the 
thorax  and  the  extensible  organs  which  it  contains,  and  on  the 
other  the  expiratory  muscles  are  assisted  in  their  action  by  the 
same  conditions  which  hinder  the  action  of  the  former,  we  must 
(notwithstanding  that  the  manometric  value  of  the  pulmonary 
pressure  indicates  a  greater  effect  of  the  expiratory  than  of  the 
inspiratory  muscles)  assume  that  the  latter  develop  a  distinctly 
greater  amount  of  energy  than  the  former. 

The  oscillations  of  pressure  along  the  respiratory  tract  may  be  used  in 
man  as  in  other  animals  for  recording  tracings  of  respiratory  movements. 
The  simplest  method  is  to  introduce  one  end  of  a  tube  into  the  nasal  cavity 
or  the  mouth,  and  to  attach  the  other  to  a  Marey's  tambour.  With 
animals  it  is  more  convenient  to  insert  a  two- way  cannula  into  the  trachea, 
one  arm  of  which  communicates  freely  with  the  external  air,  while  the  other 
is  connected  by  a  rubber  junction  with  the  tambour.  By  constricting  or 
distending  the  lumen  of  the  tube  through  which  the  animal  breathes,  a 
greater  or  less  fraction  of  the  oscillations  of  pressure  in  the  trachea!  air  can 
be  recorded  on  the  registering  apparatus. 

A  better  and  more  exact  method  is  that  of  making  the  animal  breathe 
into  a  very  large  vessel,  communicating  on  the  one  hand  with  the  trachea, 
on  the  other  with  a  writing  tambour  (Bert),  or  with  a  small  and  very 
sensitive  spirometer  provided  with  a  writing  point  that  records  the  excursions 


XII 


MECHANICS  OF  RESPIRATION 


425 


on  the  rotating  cylinder  (Tigerstedt),  as  shown  in  Fig.  187.  The  chamber  in 
which  the  animal  breathes  must  be  entirely  shut  off  when  it  is  desired  to 
trace  the  progressive  alterations  in  the  respiratory  movements  due  to 
asphyxia  (Luciani) ;  otherwise  it  communicates  with  the  outer  air  by  a  more 
or  less  open  tube,  which  allows  the  air  within  the  bottle  to  be  renewed  when 
required  (Tigerstedt).  In  that  case,  however,  the  oscillations  in  the  tracing 
are  not  proportional  with  those  of  the  intrapulmoiiary  pressure. 

The  same  effect  may  be  obtained  when  the  animal  is  breathing  free 
air,  while,  enclosed  within  a  hermetically  sealed  glass  cylinder  (Knoll). 
A  tube  tied  in  the  trachea,  or  fitting  closely  over  the  mouth  and  nostrils 
of.  the  animal,  passes  through  one  wall  of  the  box  and  communicates  with 
the  external  air.  The  internal  air  of  the  box  is  connected  by  means  of  a 
second  tube  with  a  recording  tambour,  and  traces,  like  a  plethysmograph, 
the  variations  in  the  total  volume  of  the  animal,  corresponding  to  the 
iuspiratory  and  expiratory  movements.  The  simplest  application  of  this 
method  is  that  of  Bernstein,  represented  in  Fig.  188. 

IX.  Iii  proportion  as  the  negative  in tra thoracic  pressure 
increases  or  diminishes  in  consequence  of  the  inspiratory  and 
expiratory  movements,  the 
lungs  dilate  and  retract 
with  the  air  that  pene- 
trates through  the  glottis 
to  the  pulmonary  passages, 
where  equilibrium  of  air 
pressure  is  restored. 

Both  in  dilatation  and 
•in  retraction  of  the  lungs 
the  two  layers  of  the 
pleura,  visceral  and  parie- 
tal, remain,  as  we  have  said 
in  constant  contact.  At  the 
same  time  they  glide  one  over  the  other,  because  the  cavity  of  the 
thorax,  owing  to  the  action  of  the  respiratory  muscles,  does  not 
dilate  and  contract  equally  in  all  its  diameters,  but  undergoes 
perceptible  changes  of  form,  particularly  at  the  base,  so  that  the 
lungs  (which  must  passively  follow  the  excursions  of  the  thorax) 
also  change  their  form  in  order  to  adapt  themselves  to  the  new 
shape  of  the  thoracic  cavity  (Bonders). 

The  most  immovable  part  of  the  lungs,  which  undergo  the 
least  displacement,  are  the  roots,  the  apices,  the  posterior  border, 
and  that  portion  of  their  external  surface  which  underlies  the 
lateral  parts  of  the  vertebral  column  ;  the  most  mobile  are  those 
farthest  removed  from  the  tixed  parts,  i.e.  their  inferior  and 
anterior  borders,  and  the  median  surfaces.  The  movement  of  the 
pleural  layers,  therefore,  takes  place  specially  in  the  longitudinal 
direction  from  above  downwards,  and  in  the  transverse  direction 
from  behind  forwards. 

Under  normal  conditions  this  movement  can  be  distinguished 
by  percussion,  which  yields  a  clear,  full  sound  in  every  part  of  the 


Fm.  188.— Bernstein's  pneumoplethysmograph  or  spiro- 
graph.  Hermetically  sealed  glass  cylinder,  in  which 
the  animal  breathes  the  external  air  freely  from  the 
mask  c  and  tube  a.  The  rubber  tube  b,  communicating 
with  the  inside  of  the  cylinder,  is  connected  withta 
Marey's  tambour  and  writing-lever. 


426 


PHYSIOLOGY 


CHAP. 


thoracic  wall  beneath  which  there  is  pulmonary  substance,  and  a 
dull  sound  where  there  are  viscera  which  contain  no  air.  The 
lower  border  extends  in  normal  expiration  from  the  sternal  margin, 
on  both  sides  almost  to  the  insertion  of  the  sixth  rib,  in  the 
axillary  line  almost  to  the  upper  border  of  the  seventh  (Fig.  189). 
The  anterior  margin  of  the  left  lung,  in  ordinary  expiration, 
reaches  the  line  that  goes  from  the  median  point  of  the  insertion 
of  the  fourth  rib  to  the  insertion  of  the  sixth  (see  line  ft"). 

In  deep  inspiration  the  inferior  borders  of  the  lungs  pass 
beyond  the  sixth  and  reach  the  seventh  rib  (see  line  mri),  posteriorly 
they  reach  the  eleventh ;  the  anterior  margin  of  the  left  lung 
comes  forward  to  the  line  ii'. 


FIG.  189. — Displacement  of  pulmonary  borders  in  respiratory  movements.  (Landois.)  The  line  atb 
indicates  the  lower  border  of  the  lungs  when  all  the  respiratory  muscles  are  at  rest.  The  line 
mn  indicates  the  right  pulmonary  border  in  deep  inspiration ;  hi  in  deep  expiration.  The 
triangle  tt't"  corresponds  with  area  of  absolute  dulness  of  heart  when  thorax  is  at  rest. 
In  deep  inspirations  this  area  is  reduced  to  the  small  triangle  fit'  owing  to  advance  of  internal 
border  of  left  lung ;  in  deep  expiration,  on  the  contrary,  the  triangle  extends  to  tee'  by  the 
retraction  of  this  border.  The  line  dd'd"  limits  the  area  of  relative  dulness  of  heart,  the  heart 
being  separated  from  the  thoracic  wall  by  a  thin  sheet  of  lung. 

In  very  energetic  expiration  the  lower  borders  of  the  lungs 
rise  to  the  line  hi ;  the  anterior  margin  of  the  left  lung  protrudes 
as  far  as  the  line  ee'. 

In  phuritis  exudativa,  when  the  pleural  layers  become 
roughened  on  the  surface,  their  friction  during  the  respiratory 
movements  gives  rise  to  a  characteristic  murmur  of  friction,  which 
the  physician  uses  in  diagnosis. 

With  direct  auscultation,  and  with  the  stethoscope,  a 
murmur  is  heard  on  inspiration  throughout  the  whole  extent  of 
the  lungs,  which  is  known  as  the  vesicular  murmur,  because  it  de- 
pends on  the  dilatations  of  the  alveoli  and  the  friction  of  the  air 
that  traverses  the  bronchioles.  The  murmur  is  rougher  in  children 
up  to  the  age  of  twelve,  because  the  pulmonary  infundibuli  are 


xii  MECHANICS  OF  RESPIRATION  427 

about  J  smaller  than  in  adults.     In  expiration  a  weak  and  c^uiet 
murmur  is  heard. 

In  auscultating  along  the  larger  respiratory  passages  (larynx, 
trachea,  great  bronchi),  both  in  inspiration  and  in  expiration  a 
harsh  murmur  is  heard,  sharp  and  clear,  resembling  the  guttural 
German  cli,  which  is  known  as  the  bronchial  murmur.  This  is 
perceptible  not  merely  in  the  neck,  along  the  larynx  and  trachea, 
but  also  in  the  thorax  between  the  two  shoulder-blades  at  the 
le.vel  of  the  fourth  dorsal  vertebra,  the  point  at  which  the  bronchi 
bifurcate.  It  is  a  little  more  accentuated  on  the  right  side, 
because  the  right  bronchus  is  of  greater  calibre  and  is  stronger  as 
a  rule  in  expiration  than  in  inspiration.  In  the  other  parts  of  the 
thorax  the  bronchial  murmur  is  imperceptible,  being  covered  by 
the  vesicular  murmur.  But  it  is  heard  distinctly  in  certain  parts 
of  the  pulmonary  area,  when  the  alveoli  are  atelectatic  or 
infiltrated.  In  pneumonia,  accordingly,  the  area  of  lung  that 
has  become  impervious  to  air,  or  hepatised,  (-an  be  determined 


FIG.  li»0. — Respiratory  oscillations  of  intruthoracic  pressure  (T)  ami  intra-abdominal  pressure  (A 
in  anaesthetised  cloy;.    (Luciaiii.) 

from  the  extent  of  the  region  in  which  the  bronchial  murmur 
is  abnormally  audible. 

X.  As  above  stated  it  is  not  only  the  lungs,  but  also  the  heart 
and  blood-vessels  that  feel  the  effects  of  the  changes  in  pressure 
determined  by  respiratory  rhythm. 

To  obtain  an  exact  knowledge  of  these  effects  it  is  necessary 
first  to  study  the  oscillations  of  intrathoracic  and  intra-abdominal 
pressure  in  the  two  periods  of  the  respiratory  cycle  or  revolution. 
This  is  most  simply  effected  by  the  method  of  the  oesophageal  or 
rectal  sound,  in  conjunction  with  Marey's  recording  tambour 
(Luciani,  1878  ;  Rosenthal,  1880). 

The  tracings  of  Fig.  190,  which  we  obtained  by  this  method 
from  an  anaesthetised  dog,  are  highly  instructive,  since  they  show 
that  the  respiratory  oscillations  of  pressure  within  the  thorax  and 
abdomen  are  not  coincident  but  interfering.  While  intrathoracic 
pressure  falls  during  inspiration  and  rises  in  expiration,  i intra- 
abdominal  pressure  rises  in  the  first  period  of  inspiration  and 
falls  in  the  second,  and  falls  in  the  first  period  of  expiration  and 


428  PHYSIOLOGY  CHAP. 

rises  again  in  the  second.  To  interpret  these  facts  it  is  necessary 
to  assume  that  the  diaphragm  intervenes  actively  only  in  the  first 
period  of  inspiration,  and  that  the  abdominal  muscles  intervene 
actively  only  in  the  second  period  of  expiration.  This  agrees  with 
what  was  stated  above  as  to  the  relative  inspiratory  importance 
of  the  external  intercostal  muscles,  and  the  constantly  active 
character  of  the  expiratory  movements. 

The  respiratory  oscillations  of  pressure  in  the  two  great 
body  cavities  are  the  more  ample,  or  extensive,  in  proportion  as 
the  entrance  and  exit  of  air  from  the  pulmonary  passages,  which 
tends  to  compensate  them  and  to  re-establish  equilibrium,  is  more 
difficult.  This  fact  can  be  experimentally  verified  by  recording 
the  tracings  of  intra-abdoniinal  pressure  in  a  tracheotomised  animal, 
and  observing  how  the  respiratory  curves  are  modified  when  the 
lumen  of  the  tube  attached  to  the  tracheal  cannula  is  constricted. 
Fig.  191  shows  that  the  effect  consists  more  particularly  in  a  con- 
spicuous exaggeration  of  the  inspiratory  acts,  which  become  deeper 


FIG.  191. — Respiratory  oscillations  of  intratliuracR-  pressure  (T)  and  intra-alxlominal  pressure  (A) 
in  anaesthetised  and  traclieotomised  dog.     At  B  the  tracheal  tube  was  constricted.     (Lnciani.) 

and  longer.  Expiratory  activity  is  also  exaggerated,  but  in  a  less 
degree,  and  with  reference  solely  to  intensity  and  not  to  duration. 
The  interference  of  the  two  curves,  intrathoracic  and  intra- 
abdomlnal,  persists. 

The  determination  in  the  different  higher  animals,  and  in  man, 
of  the  absolute  values  of  the  respiratory  oscillations  of  intra- 
thoracic and  intra-abdominal  pressure  has  not  been  fully  worked 
out.  We  have  only  the  few  data  obtained  on  the  rabbit  from 
Adamkiewicz  and  Jacobson,  and  those  of  Kosenthal,  which  show 
that  in  this  animal,  in  normal  inspiration,  the  pressure  falls 
to  -  40  mm.  water  ( =  -  3  mm.  Hg),  and  that  in  the  most  intense 
inspirations,  with  closed  trachea,  the  negative  pressure  may  amount 
to  -  250  mm.  water  (  =  -  20  mm.  Hg). 

More  recently  certain  observers  (Ewald,  Einthoven,  Aron,  van 
der  Brugh)  have  succeeded  by  means  of  a  special  apparatus  (with- 
out causing  pneumothorax)  in  introducing  into  the  pleural  cavity 
a  cannula  attached  to  a  manometer,  and  thus  directly  measuring 
the  pressure  of  the  pleural  cavity.  Einthoven  and  his  pupil, 
van  der  Brugh,  found  during  expiration  a  negative  pleural 


XII 


MECHANICS  OF  RESPIRATION 


429 


FIG.  19± — Luciuni's  oesophageal  explorer.    Elastic 
sound,   covered  at    the  end    with    tint-  rubber 


pressure  equal  to  -  80,  during  inspiration  equal  to  -  102  mm. 
of  water. 

The  simplest  method  for  recording  the  oscillations  of  intrathoracic  preSvSiire 
in  animals  is  to  introduce  into  the  oesophagus,  after  previous  oesophagotorny, 
an  elastic  sound,  or  hollow  metal  tul>e,  covered  at  one  end  with  a  fine  rubber 
membrane,  which  is  connected  with  a  writing  tambour,  after  ligation  of  the 
oesophagus  (Fig.  192).  This  last  operation  is  necessary  to  ensure  the  perfect 
occlusion  of  the  oesophagus  above  the  exploring  sound,  Avhile  beneath  it  the 
tonicity  of  the  cardiac  orifice  is 
sufficient  to  guarantee  closure,  save 
at  the  moment  of  deglutition,  which 
rarely  occurs  in  the  narcotised 
animal.  The  imperfect  closure  of 
the  oesophagus,  after  introducing  sheath. 
the  sound  by  the  mouth  or  nostril, 

makes  it  difficult  to  obtain  these  oscillations  of  intrathoracic  pressure  in 
man  (Rosenthal).  It  might  be  possible  to  remove  this  inconvenience  by 
the  expedient  employed  bv  PM^er  and  Ludwig  in  their  pulmonary  catheter 
(Fig.  170,  p.  388). 

Bert's  method  may  be,  employed  for  recording  the  iiitra-abdomiiial  pressures. 
This  consists  in  the  introduction  into  the  rectum  of  a  glass  tube,  fixed  against 
the  anal  sphincters  by  a  kind  of  pessary  to  make  it  air-tight,  and  connected 
with  a  water  manometer  and  writing  tambour  (Fig.  193,  A).  The  inter- 
vention of  a  manometer  is,  however,  superfluous, 
and  no  special  contrivance  is  required  to  ensure 
closure  of  the  anal  orifice,  which  was  sufficiently 
guaranteed  by  the  tonic  contraction  of  the. 
sphincters.  The  same  object  can  be  effected  by 
the  introduction  of  a  short  length  of  urethra! 
catheter  of  large  diameter,  perforated  in  several 
places,;  and  provided  at  the  ends  and  centre 
with  three  circular  ridges  formed  of  rubber 
rings,  over  which  is  drawn  a  thin  membrane 
(Luciani).  This  method  is  applicable  toyman, 
and  is  invariably  successful,  so  long  as  the 

F*o.  193.— Rectal  explorers— Bert  (A)    precaution  is  taken  of  emptying  the  intestine 
and  Luciani  (B).    A,  Glass  tube,    of  t],e    faeces  accumulated  at    the   lower  end 
open   at  the   end,  which  is   in-      .-„.       -.„„    ^ 
troduced    into  the   rectum    and     (.rig.  *•«*«*}  &)• 
plugged  in  anal  aperture  by  in- 
flation of  a  hollow  elastic  pessary  -^r  r      -\\J-t  ,1  t        1     A  1 

joined  to  the  tube.   B,  Elastic  or          XL   Whatever   the  absolute   values 

metal  sound,    with    two    lateral      nf    fkpcp    nspillnfinrisj    nf    r»re»aanra    in     the* 

openings,  fitted  with  three  rubber  (  tnese  osciiiauoiis  oi  pressure  in  tne 
Covered  with  a  small  fine  two  body  cavities  determined  by  re- 
spiratory rhythm,  it  is  evident  that  they 
must  have  a  considerable  influence  on  the  centripetal  course  of 
the  blood  in  the  veins,  and  be  an  effective  aid  to  the  circulation 
as  controlled  by  the  heart. 

This  physiological  doctrine  is  fairly  ancient.  Valsalva  (1760) 
and  Haller  (1766)  seem  to  have  been  the  first  who  observed  on 
man  the  swelling  and  emptying  of  the  jugular  vein  coincident 
with  expiration  and  inspiration.  David  Barry  (1825),  from  the 
aspiration  of  coloured  fluid  along  a  tube  fastened  centrally  in  the 
jugular,  formed  an  exaggerated  notion  of  the  functional  importance 
of  inspiratory  thoracic  aspiration.  Wedenieyer  (1828)  repeated 


430  PHYSIOLOGY  CHAP. 

the  same  experiments  with  more  discretion.  Poiseuille  (1831) 
applied  his  haemodynamouieter  to  the  veins,  and  attempted  to 
reduce  to  figures  the  force  of  the  aspiration  exerted  in  the/ 
inspiratory  act,  and  to  establish  at  what  distance  from  the  thorax 
its  influence  ceases.  With  the  discovery  of  Ludwig's  Kymograph 
(1847)  began  the  series  of  researches  by  the  graphic  method,  which 
were  directed  to  the  more  exact  determination  of  the  influence 
of  respiratory  mechanics  upon  blood  pressure  in  the  veins  and 
arteries  (see  p.  242). 

In  Fig.  194  we  have  a  very  clear  representation  of  the  intra- 
thoracic  respiratory  curves  and  the  simultaneous  curves  of  blood 
pressure  in  the  vena  cava  superior.  Apart  from  the  secondary 
oscillations  which  depend  on  cardiac  rhythm  (see  Chap.  VII.  10), 
it  will  be  seen  that  the  respiratory  curves  follow  the  same  course, 
and  coincide  with  them,  apart  from  a  slight  delay  which  the  curve 
of  venous  pressure  exhibits  in  relation  to  that  of  intrathoracic 


FIG.  194. —  Respiratory  oscillations  of  intrathoracic  pressure  (T)  and  pressure  in  vena  cava  superior 
(C)  in  anaesthetised  and  tracheotomised  dog.  (Luciani.)  T,  taken  with  oesophageal  explorer  ; 
C,  with  water  manometer — both  connected, to  Marey's  recording  tambours. 

pressure,  which  is  probably  dependent  upon  the  presence  of  the 
water  manometer.  It  may  therefore  be  concluded  that  the  negative 
pressure  of  the  intrathoracic  wave  suffers  diminution  during  the 
inspiratory  act,  so  that  the  velocity  with  which  the  blood  flows 
from  the  extrathoracic  into  the  intrathoracic  vein  and  the  heart, 
increases  proportionately.  The  opposite  occurs  during  the  ex- 
piratory act. 

When  the  effects  of  the  respiratory  movements  are  exaggerated 
by  constriction  of  the  lumen  of  the  tracheal  tube,  the  respiratory 
curves  become  more  extensive,  whether  they  are  transmitted 
from  the  oesophageal  sound  or  from  the  vena  cava  superior  (Fig. 
195). 

The  impulse  given  to  the  venous  circulation  by  the  inspiratory 
movement  is  not  counterbalanced  by  the  opposite  effect  of  the 
•expiratory  movement.  Expirations  are,  in  fact,  always  somewhat 
slower  than  inspirations;  further,  intrathoracic  pressure  always 
remains  negative  even  during  the  ordinary  expiratory  acts,  so  that 


XII 


MECHANICS  OF  EESPIEATION 


431 


it  invariably  favours  the  centripetal  course  of  the  blood  in  the 
veins :  lastly,  the  effects  of  the  respiratory  undulations  of  intra- 
abdominal  pressure  must  also  be  taken  into  consideration.  They 
are  always  favourable  to  the  course  of  the  venous  blood,  especially 
when  the  expirations  are  assisted  by  the  active  intervention  of 
the  abdominal  muscles,  as,  according  to  our  experiences,  occurs 
constantly  in  the  dog. 


FIG.  195.— Continuation  of  last  figure.     At  B  the  tube  connected  with  the  trachea  was  slightly 

constricted. 

Fig.  196  is  highly  instructive,  because  it  shows  that  the 
respiratory  undulations  of  pressure  in  the  vena  cava  inferior  are 
approximately  coincident  with,  and  present  the  same  course  as, 
those  simultaneously  traced  by  the  superior  vena  cava.  This 


Cs 


FIG.  190 — Respiratory  oscillations  of  pressure  in  vena  cava  superior  (Cs)  and  vena  cava  inferior 
(Ci)  in  chloroformed  dog.  (Luciani.)  In  Ci  the  descending  inspiratory  line  exhibits  a  pause, 
due  to  action  of  diaphragm,  which  is  not  seen  in  Cs. 

proves  the  active  intervention  of  the  abdominal  muscles,  which 
during  expiration  produce  a  pressor  effect  upon  the  inferior  vena 
cava,  while  the  action  of  the  diaphragm  during  inspiration  is  only 
capable  of  reducing  the  depressor  effect  due  to  the  relaxation  of 
the  abdominal  muscles. 

XII.  The  influence  exerted  by  the  respiratory  movements 
upon  the  pressure  and  centrifugal  course  of  the  blood  in  the 
arteries  must  necessarily  be  the  opposite  of  that  which  it  exerts 


432  PHYSIOLOGY  CHAP. 

upon  the  veins.  It  should,  however,  be  remembered  that  the 
arteries  are  not  subject  in  the  same  degree  as  the  veins  to  the 
effects  of  the  oscillations  of  intrathoracic  and  intra  -  abdominal 
pressure.  The  walls  of  the  arteries  are  in  fact  more  robust,  less 
yielding,  and  are  under  high  pressure.  They  are  more  liable  to 
the  effects  of  the  functional  modifications  of  the  heart  induced  by 
the  respiratory  movements  than  to  the  direct  consequence  of  these 
movements. 

Generally  speaking,  physiologists  in  investigating  the  re- 
spiratory waves  of  arterial  blood  -  pressure  have  arrived  at 
sufficiently  disparate  results.  This  appears  to  us  to  be  due  less  to 
fallacies  in  the  observations  or  to  the  method  employed,  than  to 
the  varying  effects  of  the  respiratory  mechanism  upon  arterial 
pressure,  according  to  the  form  and  intensity  of  respiratory 
rhythm.  This  may  be  extremely  frequent  and  superficial,  or 
extremely  infrequent  and  deep ;  and  between  these  two  extremes 


Fio.  107. — Respiratory  oscillations  of  intrathoraeic  pressure  (T)  and  pressure  in  carotid  artery 
(A)  in  a  chloroformed  dog.  (Luciani.)  Tracing  A  was  taken  with  a  Chauvean  and  Marey's 
sphygmoscope. 

many  gradations  of  form  may  be  observed,  between  which    the 
normal  type  represents  the  centre  of  the  scale. 

With  extreme  frequency  of  respiration,  arterial  pressure  does 
not  undergo  any  sensible  modification,  because  the  effects  of 
inspiration  are  obliterated  by  those  of  expiration,  which  rapidly 
succeed  them.  But  when  the  respiratory  rhythm  is  not  exces- 
sively frequent,  and  is  very  intense,  the  respiratory  undulations 
do  appear  on  the  tracings  of  arterial  pressure,  and  may  suffer  the 
same  delay,  and  coincide  approximately  with  the  waves  of 
intrathoracic  pressure.  This  is  apparent  in  the  tracings  of 
Fig.  197,  registered  on  a  chloroformed  dog,  which  in  ten  seconds 
gave  nine  profound  respirations  and  thirty-nine  cardiac  beats. 
It  will  be  seen  that  arterial  pressure  rises  at  each  expiration,  and 
falls  with  each  inspiration.  It  is  highly  probable  that  these 
results  depend  essentially  upon  exaggerated  expiratory  activity  of 
the  abdominal  muscles,  which  obstructs  the  arterial  blood-stream 
flowing  to  the  abdomen  by  compression  of  the  capillaries,  thus 
producing  indirect  rise  of  pressure  in  the  intrathoracic  arteries, 


XII 


MECHANICS  OF  KESPIKATION 


similar  to  that  which  constantly  occurs  when  the  abdominal  wall 
is  compressed  by  the  hand  along  the  course  of  the  aorta. 

When  the  respiratory  rhythm  begins  to  assume  its  normal 
form,  in  respect  of  frequency  and  intensity,  its  influence  on 
arterial  blood  pressure  diminishes  proportionally  till  it  entirely  or 
almost  disappears,  as  seen  in  the  tracings  of  Fig.  198.  A  similar 
result  was  obtained  by  Marey,  who  explained  it  by  the  antagonistic 
influence  exerted  by  the  movements  of  the  diaphragm  on  the 


FIG.  198. — Respiratory  oscillations  of  pressure  in  vena  cava  superior  (Cs)  compared  with  tracing 
of  pressure  in  carotid  artery  (Ac)  in  chloroformed  dog.     (Luciani.) 

pressure  of  the  thoracic  and  abdominal  cavities.  This  interpreta- 
tion does  not  seem  to  us  correct,  when  we  consider  on  the  one 
hand  the  secondary  part  played  by  the  diaphragm  in  respiratory 
mechanics,  and  on  the  other  the  strong  and  constant  expiratory 
activity  of  the  abdominal  muscles  as  observed  in  the  dog.  It 
suffices,  in  order  to  explain  the  small  or  negative  effect  of  ordinary 
respiratory  rhythm  on  arterial  pressure/  to  admit  that  normally 


FIG.  199. — Tracing  of  intrathoracic  pressure  (To)  and  carotid  (Cd)  in  non-anaesthetised  dog  of 
medium  size,  showing  slight  trembling,  particularly  in  expiration.    (Luciani.) 

the  respiratory  movements  are  accomplished  slowly  and  quite 
gradually,  and  that  the  abdominal  muscles  either  act  moderately 
during  expiration  (dog),  or  remain  completely  inactive  (man). 

When  the  respiratory  rhythm  becomes  very  slow  and  deep, 
a  marked  interference  is  perceived  between  the  respiratory  waves 
of  intrathoracic  pressure  and  the  respiratory  curves  of  arterial 
pressure.  This  phenomenon  was  first  illustrated  by  Einbrodt 
(1860)  in  an  excellent  publication  from  Ludwig's  laboratory. 
The  tracings  of  Fig.  199  show  the  phenomenon  in  the  most 

VOL.  i  2  F 


434  PHYSIOLOGY  CHAP. 

classical  form  in  which  it  has  ever  been  recorded.  At  the  first 
moment  of  expiration  the  arterial  pressure  rises,  falling  in  the 
second  period  ;  in  the  first  period  of  inspiration  it  continues  tp 
fall,  and  then  rises  at  the  second.  Arterial  pressure  therefore 
reaches  its  maximum  in  the  first  period  of  expiration,  and  its 
minimum  in  the  first  period  of  inspiration. 

In  explanation  of  this  fact  Einbrodt  assumes  that  the 
inspiratory  fall  of  intrathoracic  pressure,  by  determining  an 
acceleration  of  the  venous  current,  favours  the  diastolic  refilling  of 
the  heart,  which  is  followed  by  a  larger  systolic  outflow,  raising 
arterial  pressure.  This  increase  is  maximal  during  the  first 
period  of  expiration,  either  on  account  of  the  previous  excess 
filling  of  the  heart,  or  from  the  expiratory  increase  of  intrathoracic 
pressure,  which  favours  the  centrifugal  course  in  the  arteries  and 
the  systolic  action  of  the  heart.  In  the  second  period  of  expira- 
tion the  arterial  pressure  falls  owing  to  retardation  of  the  venous 
current  in  the  blood,  which  diminishes  the  diastolic  refilling  and 
systolic  emptying  of  the  heart. 

This  theory  is  inadequate,  because  it  takes  no'  account  of 
the  pressor  influence  of  the  abdominal  muscles,  which  is  capable 
of  raising  arterial  pressure  during  expiration,  by  compressing 
the  capillaries  of  the  vessels  belonging  to  the  intra-abdominal 
aortic  system. 

Funcke  and  Latschemberger  (1877)  held  the  fundamental 
cause  of  the  phenomenon  to  lie  in  the  changes  of  capacity  in  the 
capillary  pulmonary  system,  effected  by  the  alternate  dilatation 
and  retraction  of  the  lungs,  the  respiratory  oscillations  of  pressure 
in  the  thoracic  cavity  being  only  of  secondary  importance.  They 
found  in  fact  -that  in  curarised  rabbits,  during  artificial  respirations 
by  the  bellows,  with  open  thorax,  there  were  still  respiratory 
oscillations  of  carotid  pressure.  They  explained  this  fact  by 
admitting  that  when  the  alveoli  of  the  lung  dilate  (whether  from 
positive  tracheal,  or  from  negative  pleural  pressure)  the  capillary 
network  which  they  contain  must  become  stretched,  with  a 
consequent  elongation  and  constriction  of  the  vascular  lumen, 
resulting  in  a  considerable  diminution  in  their  capacity.  The 
opposite  changes  must  occur  at  each  expiratory  retraction  of  the 
pulmonary  alveoli,  which  increases  the  capacity  of  the  capillary  rete. 
Given  these  effects  of  the  respiratory  movements,  they  must  not 
merely  influence  the  course  of  the  blood  in  the  lesser  circulation, 
but.  must  also  act  indirectly  upon  the  pressure  of  the  aortic 
system,  which  is  fed  from  the  pulmonary  blood.  The  inspiratory 
increase  in  pressure  would  depend  upon  the  expulsion  of  the 
blood  from  the  compressed  pulmonary  capillary  system  into  the 
left  heart;  the  expiratory  fall  of  pressure,  on  the  retention  of  the 
blood  in  the  newly  dilated  capillaries  of  the  lungs. 

This  theory,  if  not  wholly  unfounded,  is  at  any  rate  very 


xii  MECHANICS  OF  KESPIRATION  435 

exaggerated.  The  respiratory  oscillations  of  arterial  pressure 
are  not  obtained  with  open  thorax,  unless  the  rhythmical 
pulmonary  dilatation  with  the  bellows  is  grossly  exaggerated. 
The  same  authors  constantly  observed  that  the  respiratory  waves 
of  arterial  pressure  obtained  with  closed  thorax  in  the  curarised 
rabbit,  with  a  medium  degree  of  rhythmical  insufflation,  became 
notably  weaker,  or  even  disappeared  altogether,  when  the  pleural 
cavity  was  scarcely  yet  open,  and  it  was  only  on  increasing  the 
insufflations  that  they  could  be  made  to  reappear,  or  resume  their 
former  level. 

This  fact  shows  the  predominating  importance  of  the  oscilla- 
tions of  intrathoracic  and  intra-abdominal  pressure,  as  causal 
factors  in  the  respiratory  arterial  undulations. 

Heinricius  and  Kronecker  (1888),  taking  up  Einbrodt's  experi- 
ments, showed  that  whatever  impeded  the  cardiac  diastole  lowered 


FIG.  200. — Tracings  of  intrathoracic  pressure  (To),  pressure  in  crural  artery  (Acr\  and  in  carotid 
artery  (Acn)  in  anaesthetised  dog  with  cut  phrenics.     (Luciani.) 

arterial  pressure,  and  whatever  facilitated  and  aided  the  former 
increased  the  latter.  The  influence  of  the  respiratory  movements 
of  the  filling  and  emptying  of  the  heart  would  thus  be  the  funda- 
mental condition  of  the  respiratory  waves  of  arterial  pressure. 
"  Regular  respiration,"  according  to  these  authors,  "  produces  a 
salutary  massage  of  the  heart." 

In  order  adequately  to  interpret  the  arterial  respiratory  wave, 
the  influence  which  respiratory  rhythm,  when  sufficiently  pro- 
nounced, can  exert  on  cardiac  rhythm  must  also  be  taken  into 
account.  When  the  vagi  are  highly  excitable,  cardiac  accelera- 
tion may  frequently  be  observed  in  inspiration,  and  a  delay  in 
expiration.  The  tracings  in  Fig.  200  give  a  striking  example  <ff 
this  phenomenon.  Since  this  effect  disappears  after  section  of 
the  vagi,  Einbrodt  correctly  takes  it  to  be  the  effect  of  a  reflex 
rhythmical  excitation  of  the  bulbar  centre  of  the  cardiac  vagi 
during  the  expiratory  acts. 


436  PHYSIOLOGY  CHAP. 

XIII.  It  is  easy  from  the  above  to  deduce  the  beneficial  influ- 
ence of  the  respiratory  mechanism  upon  the  circulation  of  the  blood 
(and  lymph),  as  shown  more  particularly  in  the  aspiration  exerted 
by  the  thorax  during  inspiration,  which  accelerates  the  centripetal 
current,  and  increases  the  filling  of  the  heart.  This  inspiratory 
influence  cannot  be  eliminated  by  the  contrary  effects  of  the 
expiratory  movements,  particularly  when  the  abdominal  muscles 
intervene  actively,  as  has  constantly  been  verified  on  certain 
animals. 

Some  observers,  however,  particularly  Filippo  Pacini  in  Italy, 
have  exaggerated  the  importance  of  the  respiratory  mechanism  on 
the  circulation  of  the  blood,  contending  that  a  drowned  person 
whose  cardiac  movements  have  practically  ceased,  can  be  brought 
back  to  life  merely  by  artificial  respiration.  The  untenability  of 
this  view  is  shown  by  two  classical  experiments,  one  devised  by 
Valsalva  (1740),  the  other  by  Johannes  Miiller  (1838),  which 
consist  in  determining  what  influence  can  be  exerted  by  the 
respiratory  movements  on  the  circulation,  under  conditions  in 
which  the  respiratory  oscillations  of  intrathoracic  and  intra- 
abdominal  pressure  are  in  a  position  to  exert  maximal  influence 
upon  the  course  of  the  blood,  or  more  accurately  upon  the  entrance 
and  exit  of  the  blood  from  the  thoracic  cavity. 

If  the  glottis  is  closed  after  a  deep  inspiration,  and  a  strenuous 
and  prolonged  expiratory  effort  is  then  made,  such  pressure  can  be 
exerted  on  the  heart  and  intrathoracic  vessels  that  the  movements 
and  flow  of  the  blood  are  temporarily  arrested  (Valsalva).  Pro- 
nounced swelling  of  the  veins,  visible  principally  in  those  of  the 
neck  and  face,  evacuation  of  the  vessels  in  the  pulmonary  system, 
and  surcharge  of  the  systemic  circulation,  cessation  of  cardiac 
sounds,  and  disappearance  of  the  arterial  pulse,  can  all  be  witnessed 
(E.  H.  Weber,  Bonders). 

If  instead  of  a  forced  expiration,  the  glottis  is  closed,  and  a 
prolonged  inspiratory  movement  made,  the  heart  and  all  the  intra- 
thoracic vessels  fill  to  such  an  extent  that  the  arterial  pulsations 
cease,  owing  to  the  surcharge  of  the  lesser,  and  comparative 
evacuation  of  the  greater  circulation  (J.  Miiller). 

These  experiments  cannot  be  performed  without  a  certain 
amount  of  risk,  particularly  to  individuals  who  are  no  longer 
young,  and  whose  cardio- vascular  system  is  no  longer  vigorous  and 
functioning  normally.  They  may,  however,  be  conveniently  re- 
produced on  an  artificial  schema  which  represents  the  thoracic 
cavity,  lungs,  heart,  and  related  vessels,  as  shown  in  Fig.  201. 

The  results  of  these  researches  show  that  the  respiratory 
movements  are  only  favourable  to  the  circulation  of  the  blood 
when  they  are  performed  quietly,  in  a  normal  manner  and  with  open 
glottis,  so  as  not  to  disturb  cardiac  activity,  or  compress  or  dilate 
the  heart  to  any  extent.  It  is  then  seen  (as  can  readily  be  con- 


XII 


MECHANICS  OF  KESPIEATION 


437 


firmed  on  the  schema)  that  the  inspiratory  movements  assist  the 
venous  (and  lymphatic)  current,  and  favour  the  diastolic  filling  of 
the  heart,  while  the  expiratory  movements  facilitate  the  arterial 
current  and  systolic  evacuation  of  the  heart. 

XIV.  The  rhythmical  respiratory  movements  suffer  various 
modifications,  in  abnormal  or  unusual  conditions,  or  to  satisfy 
various  temporary  needs  or  occurrences,  or,  lastly,  as  the  motor 
expression  of  special  sentiments  of  pleasure  or  pain,  fatigue,  ennui, 


FIG.  201.— Schema  to  demonstrate  effect  of  strong  positive  and  negative  intrathoracic  pressures 
upon  heart  and  blood-stream.  (Landois.)  D,  U',  stout  elastic  membrane  which  closes  the 
floor  of  a  bell-jar,  and  can  be  pushed  up  or  down  by  a  handle,  to  imitate  expiration  and 
inspiration.  P,  P,  and  P'  P',  two  thin  rubber  balloons,  to  imitate  the  lungs,  communicating 
with  a  central  tube,  representing  the  trachea,  which  passes  through  the  centre  of  the  bell- 
glass,  with  tap  r  to  simulate  the  glottis.  CC',  a  rubber  ball,  to  represent  the  heart,  com- 
municating on  one  side  with  the  tube  V,  V,  which  represents  the  afferent  vessels  of  the  heart 
(provided  with  a  valve  that  opens  in  inspiration  and  closes  in  expiration),  on  the  other  with 
the  tube  A,  A',  representing  the  efferent  artery,  (with  valve  that,  closes  in  inspiration  and 
opens  in  expiration).  When  r  is  closed,  the  manometer  M  shows  a  marked  diminution  of 
pressure,  with  dilatation  of  heart  and  lungs,  in  inspiration  ;  in  expiration  it  shows  marked 
increase  of  pressure,  while  the  heart  and  lungs  retract. 

sleep,  etc.  The  principal  forms  may  be  briefly  summarised  as  an 
appendix  to  the  mechanics  of  respiration. 

When  there  are  mechanical  impediments  to  the  thoracic  or 
abdominal  respiratory  movements,  e.g.  plaster  bandages  applied  to 
the  chest  or  epigastrium,  the  activity  of  the  diaphragm  or  the 
levator  muscles  to  the  ribs,  respectively,  is  exaggerated,  and  the 
rhythm  becomes  deeper  and  slower. 

When  the  respiratory  movements  cause  or  increase  pains  in 
the  thorax  or  abdomen,  respiratory  rhythm  becomes  more  frequent 
and  superficial. 

Where  there  is  morbid  stenosis  of  the  air-passages,  the  respira- 
tions become  deeper  and  less  frequent.  In  pneumonia  or  pleurisy, 


438  PHYSIOLOGY  CHAP. 

with  effusions  into  the  pleural  cavity,  both  frequency  and  depth 
of  rhythm  are  accentuated. 

Both  secretions  and  exudations  along  the  air-passages,  as  also 
foreign  bodies,  solid,  liquid,  or  gaseous,  which  penetrate  them, 
readily  produce  a  reflex  cough.  This  consists  in  loud,  expiratory 
efforts,  which  produce  enforced  opening  of  the  previously  closed 
glottis,  and  by  means  of  which  the  irritant  is  expelled.  Coughing 
may  be  voluntary,  and  even  when  the  cough  is  involuntary,  it  can 
be  moderated  and  even  inhibited  by  the  will. 

The  presence  of  mucus,  of  foreign  bodies,  or  of  substances  which 
irritate  the  nasal  mucosa,  may  give  rise  to  sneezing,  which  consists 
in  one  or  more  sudden  and  noisy  expirations  through  the  nasal 
passages,  preceded  by  profound  inspirations.  In  sneezing,  the 
glottis  is  always  open,  the  posterior  nares  are  constricted  by  the 
rise  of  the  soft  palate,  the  mouth  is  seldom  open.  It  is  invariably 
a  reflex  act,  which  can  only  be  imitated  imperfectly  by  the  will ; 
it  can,  however,  be  voluntarily  modified.  The  use  of  snuff  makes 
the  nasal  mucosa  insensitive  after  a  few  days,  and  suppresses 
sneezing. 

Noisy  crying,  such  as  is  frequent  in  childhood  and  youth,  as 
the  expression  of  physical  and  moral  pain,  consists  in  short  and 
spasmodic  inspirations,  followed  by  prolonged  expirations,  with 
constricted  glottis,  relaxed  muscles  of  face  and  jaw,  simultaneous 
flow  of  tears  and  emission  of  high,  inarticulate,  laryngeal  sounds. 
Sometimes  it  is  associated  with  sobbing,  which  consists  in  repeated 
contractions  of  the  diaphragm,  producing  sudden  closure  of  the 
vocal  cords,  with  a  characteristic  and  quite  involuntary  sound. 

Noisy  laughter,  the  expression  of  sudden  pleasant  and  un- 
expected sensations,  or  of  hysteria,  consists  in  short  and  rapidly 
succeeding  expiratory  efforts  through  the  vocal  cords,  which  are 
now  brought  close,  and  now  separated,  producing  high,  clear,  and 
inarticulate  tones,  with  trembling  of  the  soft  palate.  The  mouth 
is  generally  open,  and  the  facial  muscles  contract  in  a  characteristic 
manner.  Laughter  can  easily  be  imitated  at  will,  and  to  a  certain 
extent  can  be  voluntarily  suppressed  or  moderated. 

Yawning,  the  external  expression  of  ennui,  drowsiness,  hunger, 
consists  in  a  long,  deep  inspiration,  in  which  many  of  the  accessory 
inspiratory  muscles  participate,  while  the  mouth,  fauces,  and 
glottis  open  convulsively.  Inspiration  is  followed  by  a  shorter 
expiration,  and  the  two  acts  are  accompanied  by  prolonged 
characteristic  sounds,  and  by  a  general  stretching  of  the  arms  and 
trunk.  It  is  always  an  involuntary  modification  of  breathing, 
easily  imitated  by  the  will. 


xii  MECHANICS  OF  EESPIEATION  439 


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R.  0.  WARD.     Alveolar  Air  on  Monte  Rosa.     Journ.  of  Physiol.,  1908,  xxxvii. 

378-389. 

J.  S.  HALDANE  and  E.  P.  POULTON.  The  Effects  of  Want  of  Oxygen  on  Respira- 
tion. Journ.  of  Physiol.,  1908,  xxxvii.  390-407. 


CHAPTEK  XIII 

THE   NERVOUS    CONTROL   OF   RESPIRATORY    RHYTHM 

CONTENTS. — 1.  Motor  nerves  to  respiratory  muscles  and  smooth  muscle  cells  of 
bronchi.  2.  Bulbar  respiratory  centres  and  their  localisation.  3.  Spinal  respira- 
tory centres.  4.  Cerebral  respiratory  centres.  5.  Each  of  these  centres  results 
from  the  association  of  an  inspiratory  and  an  expiratory  centre,  which  function 
rhythmically  and  alternately.  6.  Automatic  regulation  of  normal  respiratory 
rhythm,  by  afferent  pulmonary  fibres  of  vagus.  7.  Influence  exerted  on  respiratory 
rhythm  via  the  cerebral  tracts  and  sensory  nerves  in  general.  8.  Phenomena 
consequent  on  the  separation  of  the  bulb  from  the  brain  and  spinal  cord.  9. 
Dyspnoea  and  its  different  forms.  10.  Eupnoea  or  normal  quiet  respiration.  11. 
Experimental  apnoea  from  artificial  respiration  with  the  bellows.  12.  Foetal  apnoea, 
and  the  analogous  forms  of  experimental  apnoea  that  can  be  produced  in  the  adult. 
13.  Voluntary,  as  compared  with  experimental  apnoea.  14.  Apnoea  produced 
by  continuous  ventilation  in  birds.  15.  Periodic  respiration,  or  Cheyne-Stokes 
phenomenon.  16.  Physiological  theory  of  respiratory  rhythm.  Bibliography. 

THE  previous  chapter  shows  that  the  respiratory  processes  are 
highly  complex,  owing  to  the  number  of  muscles,  anatomically 
very  distinct,  and  even  remote  from  each  other,  which  co-operate 
in  them.  Their  efficacy  in  determining  the  rhythmical  dilatation 
and  constriction  of  the  thoracic  cavity,  and  consequent  pulmonary 
ventilation,  which  are  indispensable  to  life,  is  entirely  due  to  co- 
ordination, i.e.  to  the  harmonious  association  and  sequence  of  the 
contractions  of  the  individual  inspiratory  and  expiratory  muscles. 
If,  for  example,  the  external  intercostals  were  to  contract  before 
the  scaleni,  or  if  the  diaphragm  became  active  along  with  the 
internal  intercostals,  no  adequate  renewal  of  pulmonary  air  would 
.  be  obtained  except  with  a  useless  expenditure  of  energy. 

Since  the  rhythmical  activity  of  respiration  results  from  the 
co-ordinated  functions  of  many  and  very  distinct  muscles,  it  cannot 
be  founded  (as  that  of  the  heart  may  possibly  be),  on  a  physio- 
logical property  inherent  in  the  muscles,  but  must  necessarily 
depend  (as  the  facts  prove  clearly)  upon  the  rhythmical  co- 
ordinating function  of  complex  nervous  processes,  which  are  the 
subject  of  the  present  chapter. 

I.  the  nervous  mechanisms  on  which  the  respiratory  rhythm 
depends  are  as  follows : — 

(a)  Motor  nerves  to  the  individual  muscles  which  take  part  in 
the  inspiratory  or  expiratory  movements ; 

440 


CHAP,  xiii  KESPIKATOKY  KHYTHM  441 

(&)  A  central  organ,  or,  better,  a  complex  of  nerve  centres, 
interassociated,  and  constituting  a  small  system  ; 

(c)  Afferent  nerves  capable  of  modifying,  directly  or  indirectly, 
the  activity  of  the  said  centres. 

The  motor  nerves  to  the  muscles,  which  normally  determine 
inspiratory  expansion  and  expiratory  retraction  of  the  thorax,  all 
arise  in  the  anterior  roots  of  the  spinal  nerves.  The  motor  nerves 
to  the  scaleni  emerge  from  the  cervical  tract,  more  exactly  from 
the  second  to  the  seventh  nerves,  and  thus  form  the  cervical  and 
brachial  plexus,  from  which  the  branches  to  the  muscles  are  given 
off.  The  phrenic  nerves  which  serve  the  diaphragm  take  origin 
specially  in  the  fourth  cervicals,  but  are  reinforced  by  fibres  from 
the  third  and  also  from  the  fifth  pairs.  The  levatores  costarum 
longi  et  breves,  the  external  and  internal  intercostals,  and  the 
abdominal  muscles  receive  nerves  from  the  thoracic  pairs  of  the 
spinal  cord  :  and,  in  particular,  the  rami  posteriores  of  the  dorsal 
nerves  serve  the  levatores  costarum ;  the  intercostal  nerves,  the 
muscles  of  the  same  name ;  and  the  internal  or  anterior  branches 
of  the  intercostals,  the  muscles  of  the  abdomen,  which  also  receive 
fibres  derived  from  the  first  lumbar  pair. 

Physiological  proof  of  these  morphological  data  is  afforded  by 
the  following  experiments.  A  transverse  section  through  the 
spinal  cord  below  the  exit  of  the  last  intercostal  nerve  leaves  all 
respiratory  movements  entirely  unaffected,  while  a  cross-section 
in  the  thoracic  cord  paralyses  all  the  respiratory  muscles,  the 
nerves  of  which  arise  below  the  section.  When  the  lower  part  of 
the  cervical  cord  is  transversely  divided,  i.e.  above  the  first  inter- 
costal and  below  the  exit  of  the  fifth  cervical  nerves,  all  the 
motor  muscles  of  the  ribs  are  paralysed  (with  the  partial  excep- 
tion of  the  first  two,  which  are  raised  by  the  scaleni^  so  that  the 
respiratory  movements  are  effected  almost  exclusively  by  the 
rhythmical  activity  of  the  diaphragm  (Fig.  86,  p.  229).  If  the 
results  of  this  operation  are  compared  with  those  following  the 
section  of  the  phrenic  nerves  (Fig.  202),  they  show  the  extreme 
functional  importance  of  the  intercostal  as  compared  with  the 
diaphragmatic  muscles — paralysis  of  the  latter  being  in  no  way 
dangerous  to  the  life  of  the  animal,  save  in  the  case  of  young 
rabbits,  in  which  the  thorax  is  not  sufficiently  rigid,  nor  the 
thoracic  muscles  sufficiently  developed,  to  allow  of  ready  compen- 
sation for  the  failure  of  the  diaphragm.  These  observations  are 
confirmed  by  those  made  on  the  human  subject,  which  show  that 
after  paralysis  of  the  diaphragm  the  respirations  become  somewhat 
more  frequent,  but  are  accomplished  solely  by  the  muscles  to 
the  ribs  with  no  active  co-operation  of  accessory  muscles. 

When  the  section  through  the  cord  is  made  above  the  exit 
of  the  third  cervical  nerves,  as  far  as  the  apex  of  the  calamus 
scrip torius,  all  the  respiratory  muscles  properly  so-called  are 


To 


442  PHYSIOLOGY  CHAP. 

paralysed,  including  those  of  the  diaphragm,  and  only  the 
rhythmical  movements  of  the  glottis  and  the  muscles  of  the  lips 
and  nose  persist,  which,  as  we  have  seen,  not  infrequently  accom-^ 
pany  the  rhythmical  movements  of  the  thorax.  These  muscles 
are  served  by  nerves,  which  emerge  from  the  medulla  oblongata ; 
the  muscles  of  the  lips  and  nose  receive  branches  from  the  facial 
nerve,  and  the  muscles  of  the  larynx  are  innervated  by  branches 
of  the  vagus  (the  crico-thyroid  muscle  from  the  superior  laryngeal, 
and  the  rest  of  the  laryngeal  muscles  from  the  inferior  laryngealjf 
The  vagus  also  provides  the  motor  nerves  to  the  smootn 
muscles  of  the  bronchial  tubes.  This""was  lirst  demonstrated  by\ 
LSnget"(i^42);  it  was  subsequently  contested,  and  finally  confirmed 
by  the  later  experiments  of  Bert,  Schiff,  Gerlach  and  others.  The 
fact  that  stimulation  of  the  peripheral  trunk  in  certain  kinds  of 
animals  reduces  the  volume  of  the  lung,  which  can  only  be  due 
to  the  contraction  of  the  smooth  muscles  of  the  bronchi,  is  very 


FIG.  202. — Effect  of  dividing  phrenics  in  dog.  (Lnciani.)  To,  intrathoracic  pressure  ;  Ca,  carotid 
pressure.  A-B,  previous  to  section  of  phrenic ;  B-C,  after  section.  The  tracing  shows  that 
both  inspiratory  and  expiratory  movements  are  exaggerated  after  section. 

striking.  Eoy,  with  Brown,  and  Sandmann  claimed  to  have  also 
discovered  dilator  bronchial  fibres  in  the  vagus,  the  action  of 
which  is  expressed  by  pulmonary  dilatation,  when  the  peripheral 
end  of  the  vagus  is  excited  with  strong  currents.  It  is  not 
improbable  that  the  presence  of  these  dilator  fibres  in  many  cases 
weakens  or  nullifies  the  effect  of  the  simultaneous  excitation  of 
the  constrictor  fibres,  which  would  account  for  the  negative  result 
obtained  by  some  observers. 

Division  of  the  vagi  in  the  horse  causes  a  considerable  increase 
of  volume  in  the  lung,  a  proof  that  the  constrictor  fibres  of  the 
bronchi  in  these  animals  are  in  constant  or  tonic  excitation.  In 
dogs,  on  the  contrary,  section  of  the  vagi  produces  a  scarcely 
perceptible  dilatation  of  the  lung,  showing  that  there  is  only  weak 
tonic  excitation. 

According  to  some  interesting  observations  of  Fano  and  Fasola, 
the  lungs  of  the  marsh  tortoise  are  capable  of  very  extensive 
active  movements,  due  partly  to  the  smooth  muscle  cells  which 


xiii  EESPIEATOEY  EHYTHM  443 

are  innervated  by  the  vagus,  partly  to  the  striated  fibres  derived 
from  the  muscles  of  the  diaphragm,  which  penetrate  the 
parenchyma  of  the  lungs,  to  invest  the  large  alveoli,  and  are 
innervated  from  the  spinal  nerves.  When  the  vagus  is  stimulated 
in  the  neck  of  this  animal,  a  curve  of  slow  prolonged  contraction 
is  obtained  from  the  lung,  exactly  similar  to  that  served  up  by 
smooth  muscle.  When,  on  the  other  hand,  the  spinal  cord  is 
excited,  a  rapid  pulmonary  contraction  results,  which  is  evidently 
due  to  the  striated  muscles. 

The  physiological  function  of  the  smooth  muscles  of  the- 
^bronchi,  and  of  the  constrictor  and  dilator  nerves  which  serve 
them,  is  not  yet  fully  explained.  It  seems  obvious  that  they  give 
greater  resistance  to  the  bronchial  walls,  and  reinforce  this  resist- 
ance by  their  contraction,  when  the  negative  intrathoracic  pressure 
falls  too  low,  during  forced  inspiration.  Probably  the  development 
of  the  pulmonary  emphysema  is  promoted  by  atony,  or  by  the 
paresis  or  paralysis  of  the  smooth  muscles. 

II.  As  a  whole  the  central  mechanisms,  from  which  the 
several  motor  nerves  to  the  respiratory  muscles  receive  their 
rhythmical  impulses,  must  be  excessively  complicated,  seeing  that 
the  co-ordination  of  the  inspiratory  and  expiratory  movements, 
i.e.  the  harmonious  and  synergic  contraction  of  the  muscles  which 
alternately  expand  and  contract  the  thorax,  depend  upon  them. 
The  immediate  centres  for  the  motor  respiratory  nerves  must, 
however,  be  distinguished  from  the  true  controlling  and  co- 
ordinating respiratory  centre.  The  former  lie  in  the  cervico- 
dorsal  tract  of  the  spinal  cord,  and  are  formed  from  the  grey 
matter  of  the  anterior  horns,  which  contains  the  nerve  cells  of 
which  the  nerves  to  the  respiratory  muscles  are  the  prolongation  ; 
the  second  is  situated  in  the  medulla  oblongata,  and  has  probably 
no  direct  influence  upon  the  muscles,  but  is  confined  to  exciting 
and  regulating  the  functions  of  the  former. 

When  the  brain  is  extirpated  to  the  level  of  a  plane  which 
.  passes  along  the  inferior  limit  of  the  pons,  or  when  a  section  is 
made  at  the  level  of  this  plane,  it  will  be  seen  that  after  temporary 
disturbance  the  animal  continues  to  breathe  spontaneously,  in  a 
regular  and  perfectly  co-ordinated  manner.  This  experiment 
proves  that  the  co-ordinating  centre  for  the  respiratory  movements 
does  not  lie  higher  than  the  spinal  bulb.  When,  on  the  contrary, 
the  bulb  is  divided  from  the  cervical  cord  at  the  apex  of  the 
calamus  scriptorius  by  a  transverse  section,  the  respiratory  move- 
ments ipso  facto  come  to  a  standstill.  This  proves  that  the 
respiratory  centre  lies  within  that  section  of  the  bulb  which  is 
situated  between  the  two  planes  of  division  indicated. 

Which  portion  of  the  bulb  is  it,  however,  which  represents 
the  respiratory  centre  ?  The  experiments  directed  towards  the 
localisation  of  this  centre  have  a  very  involved  history,  which 


444  PHYSIOLOGY  CHAP. 

must  be  recapitulated  in  its  principal  headings.  Galen  already 
knew  that  a  section  through  the  highest  part  of  the  cord  produced 
the  immediate  death  of  the  animal.  "  Perspicuum  est,  quod  si 
post  primam  aut  secundam  vertebram,  aut  in  ipso  spinalis  medullae 
principio  sectionem  ducas,  repente  animal  corrumpitur"  (De 
anat.  administr.  lib.  viii.  cap.  ix.). 

This  experiment  was  successfully  repeated  in  1760  by  Lorry, 
arid  perfected  in  1811  by  Legallois,  who  at  a  later  time  showed 
experimentally  on  the  rabbit  that  "  respiration  depends  upon  a 
very  circumscribed  region  of  the  medulla  oblongata,  which  is 
situated  at  a  short  distance  from  the  occipital  sulcus,  and  near  the 
origin  of  the  eighth  or  pneumo-gastric  nerves." 

A  few  years  later  (1842)  Flourens  took  up  these  experiments 
of  Legallois,  and  endeavoured  to  localise  the  respiratory  centre 
more  exactly,  but  he  added  nothing  substantial  to  the  results  of 
Legallois.  In  a  subsequent  communication  (1851)  he  defined  as 
point,  ou  nceud  vital  a  very  minute  tract  of  grey  matter,  the  size 
of  a  pin's  head,  lying  in  the  median  line  towards  the  tip  of  the 
calamus  scriptorius,  ablation  of  which  infallibly  led  to  the 
immediate  death  of  the  animal. 

It  was,  however,  shown  by  Volkniann  (1842),  Longet  (1847), 
and  M.  Schiff  (1858)  that  the  respiratory  centre  is  a  double 
organ,  which  can  be  divided  by  a  median  longitudinal  section 
down  the  sinus  rhomboidalis  into  two  halves,  without  causing 
arrest  of  respiration  by  the  section.  After  these  publications 
Flourens  also  (1859)  recognised  that  the  nceud  vital  is  double, 
and  that  in  order  to  destroy  life  "  a  transverse  section  of  5  mm.  is 
required,  passing  through  the  centre  of  the  V.  of  grey  matter  in 
the  medulla  oblongata,"  i.e.  half  way  up  the  beak  of  the  calamus 
scriptorius. 

Longet,  and  even  more  definitely  Schiff,  endeavoured  to  show 
that  the  true  respiratory  centre  is  located  in  the  large  nucleus  of 
grey  matter  in  the  alae  cinereae,  which  lies  in  the  lower  part  of 
the  bulb,  external  to  the  nucleus  of  the  hypoglossus,  beneath  the 
floor  of  the  fourth  ventricle,  and  that  the  paths  by  which  the 
impulse  is  conducted  thence  to  the  spinal  cord  run  in  the  lateral 
bundles,  unilateral  section  of  which,  at  the  lower  level  of  the  bulb, 
or  at  the  level  of  the  second  and  third  cervical  vertebrae,  suffices 
to  produce  respiratory  paralysis  of  the  muscles  of  the  same  side 
(Schiffs  respiratory  hemiplegia).  The  animal  may  survive  this 
operation  for  weeks  and  months,  and  active  movements  of 
respiration  never  reappear  on  the  operated  side  (1854). 

This  last  fact  suffices  to  refute  Brown-Sequard,  who  in  1858 
denied  the  existence  of  a  bulbar  respiratory  centre.  In  his  opinion, 
the  sudden  death  of  the  animal  after  lesion  of  the  bulb  was  the 
effect,  not  of  paralysis  or  deficiency,  but  of  traumatic  excitation  of 
an  inhibitory  centre  or  the  paths  for  the  respiratory  movements. 


XIII 


EESPIEATOEY  EHYTHM 


445 


If  this  were  correct,  the  respiratory  hemiplegia  consequent  on 
unilateral  division  of  the  lateral  bundles  in  the  upper  cervical 
region  would  disappear  after  a  short  time.  It  is,  however,  true 
that  with  great  care  the  whole  of  the  so-called  nceud  vital  of 
Flourens,  as  also,  according  to  Schiff,  the  whole  internal  or  median 
half  of  the  ala  cinerea  can  be  destroyed,  without  producing 
permanent  arrest  of  respiration.  It  is  only  when  the  external 
half  of  the  ala  cinerea  is  separated  from  the  central  grey  matter 
that  respiration  on  the  corresponding  side  is  abolished  for  ever. 


FIG.  203.— Section  of  spinal  bulb  in  man  at  level  of  exit  ot  vagus  and  hypoglossal  nerves— from  the 
section.  (Lueiana.)  Crst  Rectiform  body ;  Nfc,  nucleus  of  funiculus  cuneatus ;  Villa,  ascending 
root  of  auditory  nerve  ;  NX,  nucleus  of  vagus,  which  appears  as  ala  cinerea  at  surface  of 
rhomboidal  sinus ;  NXII,  nucleus  of  hypoglossal ;  Nm  median  nucleus  (or  nucleus  of  funi- 
culus teres) ;  IXa,  ascending  root  of  glosso-pharyngeal  (or  funiculus  solitarius) ;  Fr,  formatio 
reticularis  ;  R,  raphe ;  SgB,  substantia  gelatinosa  Rolandi ;  Va,  ascending  root  of  trigeminal ; 
X,  vagus  ;  Na,  nucleus  ambiguus  ;  Oae,  accessory  external  olive  ;  Ooa,  accessory  anterior 
olive;  0,  olive  ;  XII,  hypoglossal;  L,  fillet;  Py,  pyramidal  bundle;  Narc,  arciform 
nucleus 

From  these  facts  (which  were  confirmed  in  the  last  years  of  his 
life  by  Schiff,  and  by  his  pupil  Girard)  we  must  conclude  that  the 
most  indispensable  part  of  the  respiratory  centre  lies  within  the 
outer  half  of  the  ala  cinerea,  bordering  on  the  median  limit  of  the 
restiform  body,  i.e.  external  to  the  dorsal  or  sensory  nucleus  of 
the  vagus  and  glosso-pharyngeal,  along  with  the  solitary  bundle, 
and  the  dorsal  and  distal  portion  of  the  formatio  reticularis 
(Fig.  203). 

In  the  year  1873  Gierke,  under  Heidenhain's  direction, 
carried  out  a  series  of  experiments  with  a  view  to  determining 


446  PHYSIOLOGY  CHAP. 

more  exactly  in  which  section  of  the  bulb  lesions  brought 
about  a  sudden  respiratory  standstill.  He  carefully  located  the 
site  of  the  bulbar  lesions  inflicted  during  the  life  of  the  animal,  by 
microscopic  examination  of  the  hardened  and  stained  preparations. 
He  found  that  the  arrest  of  the  respiratory  movements  was 
invariably  determined  by  the  division,  or  at  any  rate  the  injury,  of 
the  solitary  bundle,  which  he  regarded  as  the  respiratory  centre 
proper,  since  it  consists  of  a  column  of  small  multipolar  nerve  cells, 
mingled  with  nerve  fibres. 

Gierke's  results  do  not  contradict  those  of  Schiff,  since  it  is 
impossible  to  divide  the  solitary  bundle  without  at  the  same  time 
destroying  the  external,  deep  section  of  the  dorsal  nucleus  of  the 
vagus  or  the  nerve  fibres  descending  from  it.  It  is  only  the 
interpretation  of  the  results  that  differs. 

In  1892  Gad  and  Marinesco  published  a  series  of  interesting 
experiments  on  the  slow  and  gradual  destruction  of  the  floor  of 
the  fourth  ventricle  by  the  method  of  repeated  punctiform  cauterisa- 
tion by  fine  glass  rods,  rounded  and  heated  at  the  end,  which 
avoided  haemorrhage,  traction,  and  pressure  on  the  adjacent  parts. 
By  these  experiments,  undertaken  with  the  utmost  precaution, 
they  were  able  to  destroy  not  only  Flourens'  nceud  vital  at  the 
apex  of  the  calamus  scriptorius,  but  also  the  external  portion  of 
the  ala  cinerea,  including  the  solitary  bundle,  without  finally 
bringing  respiration  to  a  standstill.  They  frequently  noted 
respiratory  disturbances  and  even  arrest,  due  to  excitation  of 
inhibitory  paths,  which  soon  passed  off,  and  permitted  them  to 
proceed  cautiously  with  the  cauterisation.  Only  when  the  lesion 
was  prolonged  deep  into  the  formatio  reticularis  was  there  final 
arrest  of  respiration.  In  addition  to  the  respiratory  tracts, 
descending  to  the  spinal  centres,  the  formatio  reticularis  contains 
a  number  of  cells,  which,  although  few  in  number,  and  not  grouped 
into  a  nucleus,  may  very  well  as  a  whole  represent  the  respiratory 
centre.  At  the  same  time  it  is  not  necessary  to  destroy  the 
whole  of  this  formation  to  obtain  immediate  arrest  of  respiration. 

With  Deiters,  Gad  distinguished  that  part  of  the  formatio 
reticularis,  which  lies  medially  to  the  root  of  the  hypoglossus  and 
extends  to  the  raphe,  from  the  lateral  part  which  lies  outside  this 
root.  In  rabbit  it  is  only  necessary  to  injure  this  last  segment 
deeply  enough,  in  order  to  produce  permanent  arrest  of  the 
respiratory  movements.  In  the  cat,  on  the  other  hand,  the  same 
result  is  obtained  by  cauterising  the  part  which  lies  between  the 
root  of  the  hypoglossus  and  the  raphe.  In  any  case,  whatever 
segment  of  the  formatio  reticularis  is  destroyed,  it  suffices,  if  not 
to  bring  about  total  arrest  of  the  respiration,  invariably  to  produce 
a  considerable  weakening  in  respiratory  energy.  It  is  therefore 
probable  that  the  whole  of  the  formatio  reticularis  (which  as  a 
unit  includes  a  much  more  extensive  segment  of  the  bulb  than  the 


xni  KESPIKATOEY  EHYTHM  447 

nceud  vital  of  Flourens)  constitutes  the  bulbar  centre  of  respira- 
tion. Evidence  for  this  theory  is  given,  according  to  Gad,  in  the 
fact  that  very  circumscribed  electrical  excitation  by  means  of  fine 
needles,  varnished  as  far  as  the  points,  and  thrust  into  the  parts  of 
the  formatio  reticularis  which  lie  above  and  beneath  those  parts 
whose  destruction  produces  respiratory  arrest,  provokes  only  an 
acceleration  of  respiratory  rhythm,  and  not  a  tetanus  of  the 
inspiratory  muscles,  as  occurs  when  the  respiratory  tracts  in  the 
lateral  bundles  of  the  cervical  cord  are  excited. 

Whatever  the  extension  of  the  true  bulbar  respiratory  centre, 
it  is  certain  that  the  symmetry  of  the  respiratory  movements  on 
the  two  sides  of  the  thorax  depends  on  the  intrabulbar  commissural 
fibres,  which  unite  the  two  lateral  halves  of  the  respiratory 
centre ;  and  that  the  descending  paths,  which  unite  the  bulbar 
centre  with  the  spinal  centres  of  the  respiratory  muscles,  and  run 
directly,  without  decussating,  in  the  lateral  bundles  and  in  the 
highest  portion  of  the  cervical  region,  are  probably  located  in  the 
processus  reticularis,  which  lies  between  the  anterior  and  posterior 
horns  of  the  grey  matter  of  the  cord. 

III.  We   have   already  seen    that   Brown-Sequard,  in    1858, 
denied  the  existence  of  a  bulbar  respiratory  centre,  and  interpreted 
the  results  of  Flourens'  experiments  as  inhibitory  phenomena,  by 
which  the  rhythmic  activity  of  the  spinal  centres,  the  sole  cause 
of  the  respiratory  movements,  were  suspended.     The  successful 
destruction  of  the  so-called  nceud  vital  without  abolishing  respira-  I 
tion  seemed  to  justify  his  opinion.     Now,  however,  we  know  that  I 
the  noeud  vital   does   not   constitute   the  whole   of   the   bulbar  ; 
respiratory  centre,  which  is  much  more  extensive,  and  apparently  1 
comprises  the  entire  formatio  reticularis.  / 

In  1880  Langendorff  attempted  to  resuscitate  the  doctrine  of 
Brown-Sequard,  in  Germany,  on  the  strength  of  an  interesting  fact 
discovered  in  1874  by  P.  Eokitansky.  He  saw  that  in  young 
rabbits  it  is  possible  for  a  certain  time  to  revive  the  respiratory 
movements  suppressed  by  separation  of  the  bulb  from  the 
spinal  cord,  after  suspending  artificial  respiration  and  slightly 
strychninising  the  animal,  to  increase  the  excitability  of  the  cord. 
Schroff  confirmed  this  in  1875,  adding  that  in  order  to  reinstate 
some  respiratory  movements  in  animals  with  divided  bulb,  without 
employing  strychnine,  it  was  only  necessary  to  avoid  cooling 
during  artificial  respiration  by  keeping  the  animal  in  a  warm 
chamber.  Langendorff  (1880)-  further  found,  after  dividing  the 
bulb,  that  natural  respiration  was  reinstated  for  a  considerable 
time  in  newborn  puppies  and  kittens  without  resorting  to 
adventitious  aids  other  than  artificial  respiration.  Since  it  is 
well  known  that  in  the  newborn,  as  in  the  lower  animals,  the 
functions  of  the  spinal  cord  exhibit  a  far  greater  degree  of 
autonomy  and  independence  of  the  higher  centres  than  in  the 


448  PHYSIOLOGY  CHAP. 

adult,  Wertheinier  (in  1886)  endeavoured  in  France  to  repeat 
the  same  experiments  on  adult  animals  by  prolonging  artificial 
respiration  for  f-2  hours  after  section  of  the  bulb,  in  order  to  give 
time  for  the  supposed  traumatic  inhibition  to  pass  off.  He 
observed  that  at  the  close  of  artificial  respiration  the  animals 
made  certain  movements  of  the  thorax,  abdomen,  and  limbs,  which 
produced  a  kind  of  pulmonary  ventilation,  and  kept  them  alive  for 
a  considerable  time,  even  in  some  cases  for  three-quarters  of  an 
hour. 

On  the  whole,  no  definite  conclusions  as  to  the  independence 
of  the  spinal  respiratory  functions  from  the  bulb  can  be  deduced 
from  these  experiments.  There  is  no  proof  that  the  movements  of 
thorax  and  abdomen  observed  under  the  above  conditions  after 
division  of  the  bulb,  are  co-ordinated  like  normal  inspirations  and 
expirations ;  in  fact,  it  appears  from  Wertheimer's  own  observations 
that  they  are  irregular  and  inco-ordinate.  Often  they  are  simple 
active  abdominal  expirations,  followed  by  passive  inspirations  ;  at 
other  times  the  inspirations  are  associated  with  repeated  expira- 
tions, which  cancel  their  mechanical  effects,  and  look  like  double 
or  triple  inspirations.  Very  frequently  the  thoracic  and  abdominal 
movements  are  associated  with  other  movements  of  the  limbs,  tail, 
and  vertebral  column,  due  to  spread  of  excitation  from  the  spinal 
centres.  The  long  survival  period  in  animals  with  divided  cord 
may  also  be  due  to  the  marked  fall  of  temperature,  caused  by  the 
prolonged  artificial  respiration  by  which  the  animals  are  reduced 
to  the  poikilothermic  or  hibernating  condition,  in  which  they 
are  able  to  survive  for  a  long  time  with  minimal  renewal  of 
pulmonary  air. 

Langendorff  endeavoured  to  sustain  his  theory  of  there  being 
only  an  inhibitory  and  regulatory  centre  for  respiratory  move- 
ments in  the  bulb — their  activity  being  due  solely  to  the  spinal 
centres — by  showing  that  mechanical,  electrical,  and  chemical 
stimulation  of  the  floor  of  the  fourth  ventricle,  in  chloralised 
rabbits,  induced  phenomena  of  respiratory  arrest,  which  ceased 
with  the  excitation. 

On  the  other  hand  Kronecker  and  Marckwald  (1887-89),  on 
repeating  the  experiments  with  rabbits  in  which  the  spinal  bulb 
was  separated  from  the  cerebrum,  obtained  quite  opposite  results. 
Respiration  was  accelerated  by  electrical  stimulation  of  the  bulb, 
which  also  caused  respiratory  movements,  intercalated  between 
those  made  by  the  animal.  This  was  confirmed  by  Aducco  (1889) 
on  intact  and  non-anaesthetised  dogs,  both  with  electrical  excita- 
tion of  the  sinus  rhomboidalis  (Fig.  204),  and  with  its  chemical 
excitation  by  a  crystal  of  sodium  chloride. 

The  effects  of  applying  cocaine  to  the  bulb,  as  determined  by 
Aducco's  experiments,  are  even  more  striking.  When,  e.g.,  cocaine 
hydrochloride  (either  in  the  form  of  crystals,  or  as  a  powder  mixed 


XIII 


EESPIEATOEY  EHYTHM 


449 


with  vaseline)  is  applied  to  the  floor  of  the  fourth  ventricle,  it  is 
seen  after  a  few  seconds  or  minutes,  according  to  the  rapidity  of 
absorption,  that  all  respiratory  movements  cease  and  the  thorax  is 
fixed  in  the  cadaveric  posture.  This  paralysis  of  the  respiratory 
movements  is  preceded  by  a  brief  period  of  excitation,  in  which 
the  inspiratory  movements  are  exaggerated.  Quite  different  effects 
are  obtained  on  the  heart,  the  beats  being  accelerated  directly  after 
the  application  of  the  poison,  as  after  section  of  the  vagi,  or  intoxi- 
cation with  atropine,  an  effect  that  persists  after  the  respiratory 
standstill.  When  the  cocaine  hydrochloride  is  applied  in  the  form 
of  an  ointment,  so  that  the  poison  is  more  slowly  and  gradually 


FIG.  204.  —  Effects  of  weak  (A)  and  medium  (B)  electrical  excitation  of  spinal  bulb  in  dog. 
(Aducco.)  Excitation  from  a  to  w.  R,  Respirations  recorded  with  Marey's  pneumograph  ;  P, 
arterial  pressure  traced  with  Marey's  metal  manometer  ;  s",  seconds.  The  inspiratory  effects 
are  seen  on  both  tracings. 

absorbed,  different  phases  of  modification  may  be  distinguished  in 
the  respiratory  and  cardiac  movements.  Fig.  205  shows  the 
curves  of  normal  respiration  and  heart-beat  in  the  dog ;  there  are 
four  respirations  and  eighteen  heart-beats  in  20  seconds.  One 
minute  after  applying  the  cocaine  to  the  floor  of  the  fourth 
ventricle  the  curve  of  Fig.  206  is  obtained,  which  shows  five  less 
ample  respirations  and^tliee  beats  in  20  seconds.  Nine  minutes 
after  applying  the  poison  the  form  of  respiration  is  entirely  altered 
(Fig.  207)  and  has  become  quite  slow.  The  line  of  rest  of  the 
thorax  corresponds  with  the  extreme  inspiratory  position,  which 
is  due,  not  to  an  inspiratory  tetanus,  but  to  the  fact  that  the  ex- 
pirations only  are  active,  while  the  inspirations  are  passive,  i.e.  they 
represent  the  elastic  recoil  of  the  thorax  to  the  position  of 
VOL.  I  2  G 


450 


PHYSIOLOGY 


CHAP. 


equilibrium  at  the  close  of  expiration.  The  acceleration  of  the 
cardiac  movements  persists;  thirty-eight  beats  may  be  counted 
in  20  seconds.  Ten  minutes  from  the  commencement  of  the 


PIG.  205. — Normal  tracings  of  respiration  (R)  and  carotid  pulse  '(1})  in  a  .dog  after  exposing  the 
rhomboidal  sinus.  (Aducco.)  R,  Tracing  recorded  with  Marey's  pneumograph ;  P,  with 
Marey's  metal  manometer  ;  .<<",  with  L)eprez  signal. 

experiment  the  active  expirations  also  cease,  and  the  animal 
quickly  succumbs  to  asphyxia,  unless  artificial  respiration  with 
the  bellows  is  resorted  to. 


FIG.  206. — Same  as  preceding,  one  minute  after  applying  O'o  grm.  cocaine  ointment  to  floor  of 
4th  ventricle.    (Aducco.) 

The  paralysing  action  of  cocaine  on  the  bulbar  centres  was  con- 
firmed by  Aducco  with  the  addition  of  a  highly  characteristic 
group  of  effects;  enormous  dilatation  of  pupil,  insensibility  of 


xni  KESPIRATOEY  EHYTHM  451 

conjunctiva,  immobility  of  pupil,  inertia  and  flaccidity  of  tongue 
and  muscles  of  jaw,  suppression  of  salivary  secretions,  marked  fall 
of  temperature,  inhibition  of  swallowing  reflexes,  failure  to  vomit 
after  injection  of  apomorphine ;  lastly,  suspension  of  any  kind  of 
reaction  from  the  cocainised  bulbar  substance  to  electrical  stimuli, 
however  strong.  The  possibility  that  under  these  conditions  there 
can  be  paralysis  of  the  spinal,  as  well  as  the  bulbar  centres,  owing 
to  spread  of  the  poison,  seems  to  be  excluded  by  the  rate  at  which 
complete  arrest  of  respiratory  movements  may  occur  (less  than 
20  seconds),  as  well  as  by  phenomena  which  prove  that  the 
excitability  of  the  spinal  centres  is  maintained — e.g.  rhythmical 
contraction  and  relaxation  of  the  sphincter  on  introduction  of  the 
finger  into  the  rectum. 

These  results  led  Aducco  to  the  important  conclusion  that  a 
true  motor  centre  exists  in  the  bulb,  besides  the  inhibitory  centre 


FIG.  207. — Same  as  preceding,  after  nine  minutes'  application  of  the  drug.    (Aducco.)    Tracing 
R  shows  the  active  and  passive  inspirations.     Followed  by  complete  arrest  of  respiration. 

to  the  heart,  and  that  both  are  paralysed  by  the  local  action  of 
cocaine.  The  paralysis  of  the  cardiac  inhibitory  centre  (formed  as 
we  have  seen  by  the  nuclei  of  origin  of  the  accessory)  causes 
acceleration  of  the  beats ;  paralysis  of  the  respiratory  centre 
(constituted  in  all  probability  by  the  formatio  reticularis)  causes 
arrest  of  respiratory  movements.  Hence  it  is  the  bulbar  respiratory 
centre  that  sends  co-ordinated  rhythmical  impulses  to  the  spinal 
centres  of  the  respiratory  muscles.  These  last  centres  are,  therefore, 
incapable  of  any  rhythmical  activity,  independent  of  that  of  the 
bulbar  centre.  If  under  certain  conditions  (as  in  the  experiments 
of  Langendorff,  Wertheimer  and  others)  they  show  activity 
independent  of  the  bulb,  this  activity,  is  not  co-ordinated,  and  is 
conditioned  by  the  peripheral  or  central  stimuli,  of  which  we  have 
still  to  study  the  mechanism. 

The  simplest,  clearest,  and  most  incontrovertible  proof  of  the 
absolute   dependence   of  the   spinal   centres   of    the   respiratory 


Ts 

Td 


452  PHYSIOLOGY  CHAP. 

muscles  upon  the  controlling  bulbar  centre  appears,  however,  in 
the  fact  that  permanent  respiratory  hemiplegia  ensues  on  unilateral 
section  of  the  upper  cervical  cord  (Fig.  208).  Schiff  rightly- 
directed  attention  to  this  fact  in  his  last  work  on  the  respiratory 
centre  (1894),  in  order  to  refute  the  old  doctrine  of  A  Brown- 
Sequard  as  tentatively  revived  by  Langendorff  and  Wertheimer. 

It  is,  however,  still  uncertain  whether  we  should,  with 
Langendorff,  admit  the  existence  of  another  autonomous  inhibitory 
centre  for  respiratory  movements,  along  with  the  controlling 
centre  in  the  bulb.  Laiidergreen's  studies  on  the  circulatory  and 
respiratory  phenomena  in  asphyxia  (1897),  those  of  Prevost  and 
Stern  on  the  final  respirations  (1906),  and,  lastly,  those  of  Mosso 
on  the  asphyxial  pause,  contain  no  conclusive  arguments  for  or 
against  the  theory  of  an  inhibitory,  respiratory,  bulbar  centre. 

Patrizi  and  Franchini,  on  the  ground  of  certain  peculiarities  of 


FIG.  208.— Pneumograms  of  most  convex  part  of  right  (Ts)  and  left  (Td)  half  of  thorax  in  young 
hound,  operated  on  three  weeks  previously  by  hemisection  of  cord  at  level  of  highest  cervical 
tract.  (M.  Schiff.)  The  slight  respiratory  movements  of  the  right  half  of  the  thorax  are 
passive,  i.e.,  they  depend  on  the  aspiration  of  the  mediastinum  to  the  left  dne  to  elevation  of 
sternum. 

respiratory  arrest  from  centripetal  excitation  of  the  vagus  (1906-7), 
are  inclined  to  admit  LangendorfFs  contention.  The  question  is  a 
difficult  and  complex  one,  and  will  require  extensive  experimental 
researches  before  we  can  hope  for  its  solution. 

IV.  It  is  doubtful  whether  the  bulbar  respiratory  centre,  and 
the  spinal  respiratory  centres  scattered  along  the  cervico- dorsal 
tract  of  the  spinal  cord,  really  represent  the  whole  of  the  central 
nervous  mechanisms  which  take  an  active  part  in  bringing  about 
the  mechanical  processes  of  respiration.  In  all  probability,  we 
must,  in  addition  to  the  bulbar  and  spinal  centres,  also  admit  the 
existence  of  true  respiratory  centres  in  the  brain. 

We  know  that  the  respiratory  mechanism  can  be  modified  in  a 
variety  of  ways,  both  by  voluntary  impulses  and  by  simple 
psychical  emotions.  A  practised  singer  has  such  perfect  control 
over  his  own  respiratory  movements  that  in  expelling  the  air  from 
his  lungs  he  is  able  to  produce  the  finest  shades  of  tone  during 
expiration.  Again  in  conversation,  and  still  more  in  oratory,  the 


xin  EESPIKATOEY  EHYTHM  453 

necessity  for  breathing  is  relieved  by  devices  very  far  from  ordinary. 
The  inspirations  are  taken  at  rare  intervals,  and  are  deep  and 
quickly  completed ;  they  occur  at  irregular  intervals,  and  at 
moments  when  the  phonetic  pauses  are  effective  in  expression  ;  the 
expirations,  on  the  contrary,  are  prolonged  and  often  very  power- 
ful, since  the  expired  air  is  employed  wholly  in  the  service  of 
phonetic  expression.  So,  too,  in  sucking,  swallowing,  vomiting, 
defaecation,  and  parturition,  the  mechanics  of  respiration  (as  we 
shall  see  elsewhere)  assume  different  forms  and  attitudes.  Laughing, 
crying,  sobbing,  yawning,  represent  so  many  typical  expressions  of 
feeling,  which  all,  as  we  have  seen,  consist  essentially  in  special 
forms  of  the  respiratory,  movements.  Fear,  joy,  expectation,  pre- 
occupation, are  states  of  mind  continually  associated  with 
respiratory  changes,  which  are  conspicuous  enough,  even  if  less 
characteristic  than  the  preceding.  The  direct  control  of  the  will 
is  only  exerted  upon  the  respiratory  movements  under  quite  special 
conditions — e.g.  we  hold  our  breath  when  we  know  the  air  to  be 
foul  or  stagnant,  when  we  dive  into  water,  or  under  other  similar 
conditions. 

All  these  psychical  modifications  of  the  respiratory  rhythm  are 
governed  by  impulses  emanating  from  the  cerebral  cortex, 
particularly  from  that  region  known  as  the  motor  area.  AVhen 
this  tract  is  stimulated  electrically  in  the  dog  or  cat,  the  respiratory 
movements  are  visibly  accelerated  or  retarded,  which  depends  less 
on  the  seat  than  on  the  intensity  of  stimulation.  According  to 
Fran^ois-Franck,  strong  stimuli  retard  the  respiratory  processes ; 
weak  stimuli  accelerate  them. 

The  sub-cortical  centres  are  also  capable  of  modifying  respiratory 
rhythm.  On  exciting  the  surface  of  a  section,  at  the  level  of  the 
anterior  and  posterior  corpora  quadrigemina,  Martin  and  Bocker 
obtained  unmistakable  inspiratory  effects.  Christian!  found  the 
same  on  exciting  the  floor  of  the  third  ventricle.  When,  on  the 
other  hand,  he  excited  the  grey  matter,  at  the  entrance  of  the 
Sylvian  Aqueduct,  he  obtained  expiratory  effects. 

These  different  parts  of  the  brain  (and  probably  others  not  yet 
investigated  because  less  accessible)  affect  the  respiratory  move- 
ments, in  so  far  as  they  are  capable  of  modifying  the  rhythmical 
activity  of  the  bulbar  respiratory  centre,  with  which  they  are 
connected  by  means  of  special  descending  nerve  tracts.  Evidence 
for  this  is  afforded  in  the  fact  that  the  clean  division  of  brain 
from  bulb  at  the  level  of  the  upper  limit  of  the  pons,  has,  as  we 
have  seen,  only  a  transient  effect  on  respiratory  rhythm.  This 
shows  that  even  under  normal  conditions  the  cerebral  respiratory 
centres  take  no  active  part  in  modifying  the  impulses  sent  out 
from  the  bulbar  centre.  We  shall,  however,  see  under  what 
abnormal  circumstances  the  influence  of  the  cerebral  respiratory 
centres  is  functionally  apparent  in  its  full  importance. 


454  PHYSIOLOGY  CHAP. 

The  complete  nervous  system  on  which  the  respiratory 
mechanism  depends  may  thus  be  divided  into  three  sections :  the 
bulbar,  the  spinal,  and  the  cerebral  respiratory  centres.  From  the 
first  emanate  the  rhythmical  impulses  to  thoracic  -  abdominal 
movements  on  which  the  activity  of  the  spinal  respiratory  centres 
which  pass  the  impulses  on  to  the  muscles  depends ;  but  the 
rhythmical  activity  of  the  bulbar  centres  is  in  its  turn  regulated, 
and  may  be  modified  in  a  number  of  ways,  by  the  cerebral 
respiratory  centres. 

V.  In  order  to  form  a  more  adequate  conception  of  the  mode 
in  which  these  highly  complicated  systems  function,  it  must  be 
remembered  that  we  understand  by  the  term  respiratory  centres 
an  accumulation  of  central  mechanisms,  which  are  capable  of  a 
double  and  antagonistic  action — one  inspiratory,  which  dilates  the 
thorax,  the  other  expiratory,  which  contracts  it.  As  we  have  seen 
in  the  preceding  chapter,  both  forms  of  movement  are  active  and 
are  brought  about  under  normal  conditions  by  the  contraction  of 
antagonist  muscles;  we  cannot  regard  expiration  as  the  simple 
effect  of  inhibition  acting  upon  the  inspiratory  centres,  but  must 
further  assume  the  existence  of  true  expiratory  centres*  The 
concept  respiratory  centre  thus  implies  the  association  of  two 
centres,  which  have  an  opposite  function  in  respect  of  pulmonary 
ventilation,  and  can,  therefore,  under  normal  conditions,  only 
function  rhythmically  and  alternately. 

Not  only  must  we  recognise  the  existence  of  expiratory  centres 
as  distinct  from  inspiratory  centres  ;  on  the  ground  of  irrefutable 
observations  we  must  further  admit  that  these  centres,  while 
normally  associated  in  their  rhythmical  and  alternating  functions, 
are  yet  capable  under  abnormal  conditions,  particularly  the 
influence  of  certain  poisons,  of  functioning  independent  of  each 
other.  That  the  inspiratory  centres  may,  under  special  circum- 
stances, alone  be  active  will  readily  be  admitted  by  all  (and  these 
^  form  the  vast  majority)  who  hold  that,  normally,  inspirations, alone 
are  active.  But  it  is  also  possible  to  demonstrate  that  under 
various  other  conditions  the  converse  holds  good,  the  expirations 
,  only  being  active,  while  the  inspirations  are  passive.  In  these 
,  cases  the  inspiratory  centres  do  not  function,  and  the  expiratory 
centres  alone  perform  their  work.  Inspiration  is  effected  by  the 
elastic  recoil  of  the  thoracic  walls,  which  are  pushed  below  their 
resting  position. 

Aducco  succeeded  in  collecting  certain  observations  and 
recording  them  graphically  enough  to  establish  this  fact,  which  as 
a  contribution  to  the  theory  of  the  centres  that  control  the 
mechanics  of  respiration  is  of  no  small  importance.  The  curves  of 
Fig.  209  were  recorded  by  two  tambours  with  exploring  buttons 
(applied  to  the  sternum  and  the  linea  alba  abdominis  respectively, 
their  movements  being  transmitted  to  two  other  tambours  writing 


XIII 


EESPIEATOKY  EHYTHM 


455 


on  a  revolving  drum)  from  a  tracheotomised  dog  which  had  3 
grms.  of  chloral  hydrate  injected  in  several  doses  into  its  jugular 
vein.  Under  these  conditions  there  are  seen  to  be  a  few  active 
abdominal  expirations,  in  which  one  very  energetic  and  one 
shallow  effort  alternate  with  tolerable  regularity.  All  the 


FIG.  209.— Thoracic  (T)  and  abdominal  (A)  pneumograms  obtained  from  two  exploring  button 
tambours  on  a  dog,  after  intravenous  injection  of  8  grms.  chloral  hydrate.  (Aducco.)  The 
descending  curves  of  A  correspond  to  active  abdominal  expirations.  The  slight  movements 
of  T  are  passive. 

respiratory  processes  depend  upon  these  rhythmical  abdominal 
respirations  which  pull  upon  the  thoracic  walls,  on  which  the 
traction  of  the  rectal  abdominal  muscles  follows  passively.  In 
this  case,  therefore,  the 
chloral  succeeds  (tempor- 
arily at  least)  in  paralys- 
ing the  rhythmic  activity 
of  the  thoracic  inspiratory 
and  expiratory  centres, 
while  maintaining  and 
even  increasing  the  action 
of  the  expiratory  centres 
for  the  abdominal  muscles. 
In  other  cases  (in  which 
the  specific  mechanism  of 
action  is  unknown)  the 
chloral  paralyses  both  the 
inspiratory  and  expiratory 
abdominal  centres,  and 
increases  the  rhythmical 
activity  of  the  thoracic  expiratory  centres.  Thecurvesof  Fig.  210were 
taken  from  a  tracheotomised  dog,  after  injecting  5  grms.  of  chloral 
hydrate  into  the  jugular  vein.  It  will  be  seen  that  the  resting 
position  of  the  thorax  coincides  with  the  end  of  inspiration  and 
commencement  of  expiration  ;  between  the  first  and  second  there  is 
a  pause,  after  which  a  marked  depression  of  the  thorax  occurs,  which 


pio>  210._Tracing,  as  iu  last  flgunji   Prom  dog  after 

intravenous  injection  of  5  grms.  of  chloral  hydrate. 
(Aducco.)  The  descending  lines  of  tracing  T  coincide 
with  active  thoracic  expirations,  followed  immediately 
by  the  ascending  lines  of  passive  inspiration.  The 

^verste  abdominaf  moveillents  (A)  are  passive. 


456  PHYSIOLOGY  CHAP. 

produces  a  passive  rise  of  the  abdominal  wall,  and  thus  drives  the 
air  out  of  the  trachea.  Active  thoracic  expiration  is  immediately 
succeeded  by  passive  inspiration,  in  which  the  thorax  rises  again,- 
and  the  abdomen  falls. 

These  exceptional  phenomena,  with  the  cause  of  which  we  are 
unacquainted,  and  which  accordingly  cannot  be  determined 
experimentally,  have  no  physiological  significance  other  than  that 
of  showing  the  existence  of  an  expiratory  centre,  which  can 
function  separately  when  the  inspiratory  centre  is  put  out  of  court. 
Moreover,  these  and  other  facts  investigated  by  Aducco  show  that 
in  the  dog  forced  expiration  is  no  functional  unity,  effected  always 
in  the  same  way,  and  by  the  help  of  the  same  mechanism.  It 
may  be  carried  out  by  the  walls  of  the  thorax  or  by  the  walls  of 
the  abdomen.  In  the  abdomen  itself,  according  to  Aducco,  it  is 
possible  to  separate  two  expiratory  mechanisms — the  interior  recti, 
and  the  lateral  muscles.  These  different  expiratory  mechanisms 
(thoracic,  and  anterior  and  lateral  abdominal)  may  function 
simultaneously  or  synchronously  —  or  simultaneously  and  a- 
synchronously, — or  lastly,  separately  from  one  another.  • 

Other  similar  phenomena,  noted  incidentally  by  various 
authors  (Hering  and  Breuer,  Luciani,  Stefani,  and  Sighicelli,  &c.), 
but  which  Mosso  (1878-1885)  specially  emphasised,  show  that  the 
inspiratory  centre,  too,  may  be  regarded  as  an  aggregate  of  centres, 
which,  although  they  normally  function  harmoniously,  while  each 
retains  a  certain  degree  of  autonomy  and  independence,  may  yet, 
under  certain  indefinable  conditions,  come  into  play  at  different 
times,  act  with  unequal  intensity,  and  even  be  capable  of  func- 
tioning separately.  According  to  Mosso,  we  must  at  any  rate 
accept  a  facial,  a  thoracic,  and  a  diaphragmatic  centre  for  inspira- 
tion, since  on  comparing  the  simultaneous  tracings  from  the  three 
different  groups  of  muscles,  a-synchronisms  or  different  intensities 
of  action  can  be  detected  at  different  times  upon  the  same 
individual.  The  most  striking  fact  of  this  kind  is  that  in  sleep 
respiration  is  essentially  costal,  since  (as  shown  in  another  con- 
nection, Fig.  184,  p.  418)  the  diaphragm  is  virtually  inactive.  In 
the  death-agony,  on  the  contrary,  the  opposite  prevails ;  only  the 
'diaphragm  is  active,  while  the  intercostal  muscles  are  paralysed. 
We  must  conclude  that  in  sleep  the  thoracic  and  diaphragmatic 
inspirations  coincide,  the  first,  however,  outlasting  the  second :  at 
other  times  thoracic  inspiration  precedes  the  diaphragmatic. 

From  these  and  other  similar  facts  Mosso  concluded  that  "  the 
earlier  conception  of  a  single  respiratory  centre  must  be  abandoned  ; 
the  respiratory  movements  of  the  facial  muscles,  diaphragm, 
thorax,  and  abdomen  have  their  specific  nerve  centres,  which 
function  autonomously."  Schiff,  in  his  last  work  (1894),  criti- 
cised this  attempted  decentralisation  of  respiratory  innervation. 
According  to  him  the  special  centres  of  the  spinal  cord,  on  which 


xiii  RESPIRATORY  RHYTHM  457 

depend  the  contractions  of  the  different  groups  of  muscles  that 
serve  in  respiration,  are  not  true  respiratory  centres,  since  lihey 
are  not  perfectly  autonomous,  and  require  a  co-ordinating  centre  in 
the  bulb,  which  is  the  sole  organ  on  which  respiratory  stimuli  act, 
and  is  alone  capable  of  elaborating  them  so  as  to  throw  the  spinal 
centres  into  activity.  He  opposes  the  theory  of  decentralisation 
by  one  of  centralisation.  The  difference  between  the  two  theories 
seems,  however,  to  lie  in  the  name  rather  than  in  the  conception. 
In.  our  opinion  the  real  problem  (which  has  so  far  remained 
unanswered)  is  the  more  exact  definition  of  the  nature  of  the 
co-ordinating  function  of  the  bulbar  respiratory  centre.  Do  the 
various  modes  of  functional  association  and  succession  of  the 
several  muscles  or  groups  of  respiratory  muscles  depend  exclusively 
on  this  ;  or  do  the  respective  spinal  centres  also  co-operate  actively  ; 
or  (at  the  least)  is  the  varying  degree  of  excitability  of  these  centres 
at  the  given  moment  in  which  they  receive  the  impulses  from  the 
bulbar  centre,  of  account  ? 

Nothing  definite,  again,  is  known  as  to  the  localisation  of  the 
supposed  subordinate  inspiratory  and  expiratory  centres.  We 
only  know  that  in  both  categories  we  must  distinguish  between 
the  centres  of  the  cerebral,  bulbar,  and  spinal  segments,  which 
enormously  complicates  the  problem  of  their  localisation. 

VI.  In  view  of  the  well-established  fact  that  under  normal 
vital  conditions,  with  the  senses  and  all  the  mental  emotions  at 
rest,  the  respiratory  movements  are  completed  involuntarily,  in 
consequence  of  rhythmically  alternating  impulses,  from  the 
inspiratory  and  expiratory  bulbar  centres,  the  question  arises 
whether  these  impulses  are  automatic  or  reflex  in  character,  i.e., 
whether  they  are  the  effects  of  rhythmical  changes  intrinsic  to  the 
centres,  or  depend  upon  rhythmic  or  continuous  stimuli,  coming 
to  them  from  without  ?  In  order  to  determine  this  point,  which 
is  of  fundamental  importance,  we  must  first  of  all  examine  how 
they  are  affected  by  the  various  afferent  nerves,  with  which  they 
are  in  direct  anatomical  and  physiological  relation.  Among  these 
in  the  first  place  is  the  Vagus. 

The  cervical  trunk  of  every  vagus  nerve  contains  afferent 
fibres  coming  from  the  lung,  and  passing  to  the  bulbar  respiratory 
centre.  From  the  terminal  ramifications  of  these  fibres  in  the 
lungs,  rhythmical  excitations  pass  to  the  centres,  and  are  capable 
of  throwing  them  into  activity,  or  considerably  modifying  their 
intrinsic  energy.  This  is  clear  from  the  experimental  researches 
of  Rufus  of  Ephesus,  Galen,  and  Legallois  (1812). 

When  the  trunk  of  one  vagus  is  suddenly  divided  in  the  neck, 
while  the  animal  breathes  air  regularly  from  a  large  closed  cylinder, 
connected  with  a  Marey's  writing  tambour,  which  registers  the 
oscillations  of  tracheal  pressure,  the  respiratory  type  changes  ipso 
facto ;  the  breathing  becomes  more  excursive  and  less  frequent, 


458 


PHYSIOLOGY 


CHAP. 


without  previous  suspension  of  respiration,  or  gradual  alteration  in 
the  transition  from  one  type  to  another.  The  same  effect  appears 
after  cutting  the  second  vagus,  but  in  a  more  accentuated  form ; 
immediately  after  section  the  breaths  become  extremely  dyspnoeic 
and  infrequent.  In  rabbit  these  effects  are  less  marked  than  in 
the  dog,  as  appears  from  the  curves  of  Fig.  211  (Luciani,  1879). 

-According  to  Gad  (1880)  these  results  are  not  simply  the 
expression  of  cutting  out  the  vagus  action  on  the  respiratory 
centres,  since  in  dividing  the  nerve  mechanical  stimulation  from 
the  operation  is  inevitable,  as  well  as  excitation  from  the  demarca- 
tion current  set  up  in  the  injured  trunk.  He  proposed  to  nullify 


FIG.  211.  —  Effects  of  vagus  section  on  respiratory  rhythm  on  rabbits  (AA')  and  dogs  (BB'). 
(Luciani.)  The  right  vagi  were  cut  at  TI,  the  left  at  T%.  In  A  and  A'  a  large  rabbit  breathed 
from  a  closed  vessel,  containing  12  litres  of  air.  communicating  with  a  writing  tambour. 
In  B,  B'  a  small  dog  breathed  from  a  receiver  of  30  litres  air. 

the  function  of  the  vagus,  by  lifting  it  over  a  metal  rod  cooled 
below  zero,  when  the  nerve  would  freeze  suddenly  at  the  point  of 
contact,  and  lose  its  conductivity,  without  producing  excitation. 
The  results  obtained  with  this  more  elegant  method,  however, 
differed  little  from  our  own  results  with  simple  division,  apart  from 
the  fact  that  the  inspirations  alone  became  more  ample,  while  the 
expirations  were  maintained  at  the  same  height  as  before,  or  even 
fell  below  it,  as  shown  by  Fig.  203.  Even  this  difference  was  only 
shown  in  the  rabbit ;  in  the  dog  both  inspirations  and  expirations 
were  increased.. 

These  effects,  which  follow  directly  on  the  abolition  of  vagus 
influence  upon  the  respiratory  centres,  are  not  associated  with  any 


xin  EESPIEATOKY  EHYTHM  459 

conspicuous  changes  in  the  amplitude  of  respiration,  or  degree 
of  pulmonary  ventilation  in  the  time-unit.  According  to  Gad, 
after  freezing  the  vagi  the  amplitude  of  respiration  undergoes  a 
slight  diminution ;  according  to  Lindhagen,  on  the  contrary  (in 
agreement  with  our  own  observations),  it  remains  almost  un- 
altered ;  this  means  that  the  increased  depth  of  the  respirations 
almost  perfectly  compensates  for  the  diminution  in  frequency. 

From  these  facts  we  may  deduce  the  important  conclusion 
that  the  vagi  reflexly  exert  a  marked  regulatory  influence  upon 
the  respiratory  centres.  The  respiratory  type  witnessed  after 
suppression  of  this  influence  is,  as  justly  remarked  by  Gad,  very 
ill-adapted  for  its  purpose,  since  the  respiratory  effort  is  con- 
siderably greater,  while  its  utility,  as  represented  by  the  respiratory 
volume,  is  not  increased,  and  may  even  be  diminished.  It  is  in 
fact  from  the  ratio  between  force  and  effective  utility  that  we 
must  judge  of  the  degree  of  adaptation.  If  with  intact  vagi  the 


FIG.  212.— Effect  of  freezing  the  vagus  on  respiratory  rhythm  of  rabbit.  .(Lindhagen.)  The  rabbit 
breathes  from  receiver  of  Fig.  187  (p.  422).  The  vertical  line  marks  the  moment  at  which  the 
vagi  were  frozen.  The  lower  tracing  marks  seconds. 

play  of  the  respiratory  muscles  is  modified,  this  obviously  means 
that  they  reflexly  regulate  the  respiratory  rhythm  in  such  a  way 
that  the   same   effect  is  obtained  with   far  less  effort,  and  witli- 
minimum  expenditure  of  energy. 

In  1868  Hering  and  Breuer,  in  an  important  series  of  experi-  V 
ments,  attempted  to  elucidate  the  mechanism  of  this  regulation  of 
the  respiratory  processes   by  the  vagi.     They  found  on  animals 
that  any  dilatation  of  the  lungs,  produced  no  matter  by  whaW 
means,  checked  the  inspiratory  and  promoted  the  expiratory  act ; 
whatever,   on    the   contrary,   caused    contraction    of    the    lungs,/ 
inhibited  expiration  and  determined  inspiration.     After  vagotomy, 
these  effects  ceased  altogether;  the  respiratory  rhythm  assumed 
the  type  described  above,  which  undergoes  no  modification  with 
reference  to  the  state  of  contraction  or  dilatation  into  which  the 
lungs  are  artificially  thrown.     The  results  of  Hering  and  Breuer 
may  be  recapitulated  the  better  to  define  their  effects,  and  bring 
out  their  importance  : — 


460  PHYSIOLOGY  CHAP. 

(a)  If  on  a  tracheotomised  rabbit,  with  intact  vagi,  breathing 
normally,  rhythmical  insufflations  (positive  ventilation)  or 
rhythmical  aspirations  of  air  (negative  ventilation)  are  made 
through  the  tracheal  cannula,  so  that  in  the  first  case  rhythmical 
dilatation,  and  in  the  second,  rhythmical  retraction  of  the  lungs,  is 
produced,  it  will  be  seen  that  the  animal  reacts  to  each  insufflation 
by  an  expiration,  as  plainly  shown  by  the  constriction  of  the  nasal 
pinnae,  and  to  each  aspiration  of  air  by  an  inspiration,  as  evidenced 
by  the  widening  of  the  nostrils.  If  the  insufflations  or  aspirations 
are  retarded  or  accelerated,  the  animal  adapts  its  respiration  to  the 
required  rhythm  by  making  the  opposite  movement,  i.e.  it  reacts 
with  an  expiration  to  each  dilatation,  with  an  inspiration  to  each 
contraction  of  the  lungs.  This  harmony  between  natural  and 
artificial  respiration  ceases  absolutely  after  section  of  the  vagi.  - 

(6)  If  the  rubber  ring  attached  to  the  tracheal  cannula  of  an- 
•animal  (with  intact  vagi  and  regular  respiration)  is  constricted  or 
occluded  at  the  moment  at  which  expiration  ceases  and  inspiration' 
sets  in,  it  will  be  seen  that  the  latter  lasts  far  longer.  If,  on  the 
contrary,  the  trachea  is  constricted  or  occluded  at  the  close  of  an 
inspiration  and  commencement  of  an  expiration,  the  animal  is 
seen 'to  extend  its  expirations  and  remain  longer  in  the  expiratory 
posture.  These  effects  cease  after  section  of  the  vagus.. 

(c)  When  a  ventilating  apparatus  is  attached  to  the  tracheal 
cannula  of  a  dog  or  rabbit,  which  favours  inspiration  and  hinders 
expiration,  so  that  the  extent  of  pulmonary  distension  increases  at 
each  inspiratory  act,  it  is  seen  that  the  expiratory  acts  consequent 
on  the  successive  inspirations  become  longer  and  more  energetic, 
until  the  tetanic  force  of  the  expiratory  abdominal  muscles  ejects 
the  ventilating  apparatus  from  the  cannula. 

(d)  If  in  an  animal  with  normal  respiration,  double  pneumo- 
thorax  is  suddenly  produced  by  opening  the  two  pleural  cavities, 
the  vagi  being  intact,  a  deep  and  prolonged  inspiration  follows — a 
true  inspiratory  tetanus. 

(e)  Similar  facts  are  met  with  clinically,  when  in  consequence 
of  any  kind   of  morbid  condition  the  expiratory  retraction  or 
inspiratory  dilatation  of  the  lungs  encounters  some  obstacle.     In 
the    first    case   (e.g.   in    pulmonary   emphysema)   expiration,   in 
the  second  (e.g.  stenosis  of  the  larynx  or  trachea,  plural  or  peri- 
cardial  effusions,  etc.)  inspiration,  is  prolonged. 

In  the  year  1888  Stefani  and  Sighicelli  (in  continuation  of  the 
researches  of  Hering  and  Breuer)  endeavoured  to  determine  what 
changes  in  respiratory  rhythm  occurred  when  a  rabbit  was  made 
to  pass  rapidly  from  breathing  air  under  normal  pressure  to 
respiration  at  higher  or  lower  pressures,  so  that  the  lungs  became 
passively  dilated  or  contracted.  The  method  consisted  in  applying 
a  T-cannula  with  a  three-way  tap  to  the  animal's  trachea.  One 
of  the  outer  branches  of  this  cannula  communicated  freely  with 


xiii  KESPIKATOEY  EHYTHM  461 

the  external  air,  the  other  was  connected  with  a  receiver  containing 
more  or  less  condensed  or  rarefied  air.  A  turn  of  the  tap  was 
sufficient  instantly  to  change  the  connection  of  the  lungs  from 
atmospheric  to  rarefied  or  condensed  air. 

The  results  obtained  by  this  method  do  not  seem  substantially 
to  contradict  those  of  Hering  and  Breuer.  The  transition  from 
free  to  compressed  air  provokes  a  short  or  prolonged  expiration, 
according  as  the  rise  of  pressure  causes  marked  or  slight  expansion 
of  .the  lungs.  Transition  from  free  to  condensed  air  induces  an 
inspiration  more  or  less  deep  or  prolonged,  according  as  the 
diminution  of  pressure  evokes  a  slight  or  pronounced  contraction 
of  the  lungs. 

On  the  strength  of  the  facts  enumerated  above,  Hering  and 
Breuer  propounded  the  so-called  theory  of  the  automatic  regulation 
of  respiration,  which  consists  in  the  assumption  that  the  respiratory 
movements   comprise    a    respiratory    mechanism    in    themselves, 
regulated  by  the  centripetal  fibres  of  the  pulmonary  vagi,  since 
these  excite  the  inspiratory  centres  when  the  lungs  contract,  and* 
the  expiratory  centres  when  the  lungs  expand/     In  this  way,  the 
inspiratory  state  of  the  lungs  reflexly  cuts  off'  inspiration   and 
promotes  expiration,  and    the   expiratory  state   reflexly  inhibits 
expiration  and  effects  inspiration.     Two  different  kinds  of  afferent  7 
fibres  must  be  distinguished  in  the  pulmonary  vagi — those  excited  . 
by  the  dilated  and  those  excited  by  the  contracted  state  of  the 
lungs ;  the  former  are  in  relation  with'  the  expiratory  centres,  the 
latter  with  the  inspirator/. 

The  explanation  offered  by  Stefani  is  somewhat  different. 

He  holds  that  the  inspiratory  fibres  are  stimulated,  not  by. 
pulmonary  retraction  but  by  the  fall  of  pressure  in  the  alveoli, 
and   that   the  expiratory  fibres   are  excited,  not  by  pulmonary  / 
expansion,  but  by  rise  of  pressure  in  the  alveoli.     These  smallj 
modifications  explain  why  in  cases  of  stenosis  of  the  air-passages]^ 
the  breaths  are  deep  and  infrequent  (dyspnoea),  and  why  in  cases 
of  restriction   of   the   respiratory  tract    there   are   frequent  and 
superficial  respirations  (tachypnoea).     For  in  the  first  case,  both 
inspiratory   depression    and    expiratory   rise   of    intrapulmouary 
pressure    must    be    greater,    owing    to    the    greater    difficulty 
encountered  by  the  air  in  penetrating  or  leaving  the  respiratory 
passages.      In   the    second    series    of    cases    the    conditions   are 
exactly  opposite,  so  that  the  excitation  of  both  kinds  of  vagus 
fibres  is  shorter  and  weaker. 

Confirmation  for  this  theory  of  automatic  regulation  by  the 
afferent  fibres  of  the  pulmonary  vagus  has  been  sought  in  the 
study  of  the  phenomena  consequent  on  exciting  the  central  ends 
of  the  divided  vagi.  Owing,  however,  to  the  presence  of  the  two 
antagonistic  kinds  of  fibres  in  the  vagus,  the  effects  of  its  central 
excitation  are  not  constant,  but  vary  with  the  nature  and  intensity 


462 


PHYSIOLOGY 


CHAP. 


of  the  stimuli,  so  that  the  action  now  of  the  inspiratory,  now  of  the 
expiratory  fibres  preponderates. 

*  As  early  as  1847  it  was  remarked  by  Traube,  and  later  on  by, 
Eosenthal,  that  electrical  excitation  of  the  central  end  of  a' 
vagus  cut  in  the  cervical  region  caused  excitation  of  the  inspiratory 
centres,  as  shown  by  acceleration  of  rhythm,  and  with  stronger 
stimuli  by  an  inspiratory  tetanus  (Fig.  213).  This  proves  that 
the  vagus  trunk  contains  centripetal  fibres  which  on  excitation 
act  on  the  inspiratory  centres  by  acceleration  of  their  rhythmical 


Kid.  213. — Inspiratory  effects  of  electrical  excitation  of  central  trunk  of  vagus  in  rabbit  (Fredericq). 
The  period  of  excitation  is  marked  on  the  abscissa.  The  tracing  shows  the  respiratory 
oscillations  of  pulmonary  pressure. 

impulses.  This  result,  however,  is  not  constant;  it  is  only 
necessary  to  alter  the  strength  of  the  exciting  current  in  order  to 
produce  a  diametrically  opposite  effect,  i.e.  t  slowing  of  rhythm, 
with  preponderating  expirations,  and  also  expiratory  tetanus. 
This  contrary  effect  proves  that  the  vagus  contains  other  afferent 
fibres  which  act  on  the  expiratory  centres.  If  these  are  rarely 
manifested  with  electrical  excitation  of  the  central  end  of  the 


FIG.  '214.— Expiratory  effects  of  electrical  excitation  .of  central  trunk  of  vagus  in  chloralised 
rabbit  (Fredericq).  The  period  of  excitation  is  marked  on  the  abscissa.  Eacli  stimulation  is 
followed  by  a  respiratory  arrest. 

vagus,  it  is  because  the  antagonistically  working  fibres  pre- 
ponderate. Chemical  excitation  of  the  central  end  of  the  vagus, 
however,  causes  reflexes  of  a  predominating  expiratory  nature 
(Gad).  When  the  animal  is  poisoned  with  strong  doses  of  chloral 
hydrate,  which,  as  we  have  vseen,  weakens  the  activity  of  the 
inspiratory  centres,  the  centripetal  expiratory  fibres  of  the  vagus 
come  into  play.  For  under  the.se  conditions  electrical  stimulation 
of  the  central  end  of  the  vagus  nerve  is  invariably  followed  by  an 
expiratory  tetanus,  as  appears  from  the  researches  of  L.  Fredericq 
and  Wagner  (Fig.  214). 


xni  KESPIKATOKY  EHYTHM  463 

According  to  Patrizi  and  Franchini,  the  diaphragmatic  arrest 
on  stimulation  of  the  central  trunks  of  the  vagus  is  not  invariably 
(in  profoundly  anaesthetised  animals)  the  effect  of  predominance  of 
the  excitatory  muscles,  but  may  be  merely  an  inhibitory  suspension. 
Whatever  the  phase  in  which  the  diaphragm  is  overtaken  by  the 
appropriately  graduated  stimulation  of  the  vagus,  it  becomes 
immobilised  without  change  of  tone  (level  of  record),  and  completes 
its  movement  at  the  close  of  the  inhibitory  respiratory  effect, 
resuming  it  from  the  point  at  which  it  had  been  interrupted. 
They  do  not  deny  that  excitation  of  the  vagus  may,  at  a  certain 
point,  produce  respiratory  movements,  since  they  more  than  once 
had  occasion  to  verify  that  particular  result ;  but  they  do  affirm 
that  the  respiratory  arrest  on  centripetal  stimulation  of  the  vagus 
is  not  seldom  a  merely  inhibitory  phenomenon. 

Treves  (1905)  also  admits  that  the  effects  of  faradisation  of 
the  central  end  of  the  vagus  are  inhibitory  in  character.  After 
eliminating  the  action  of  the  principal  expiratory  muscles  by 
ligature  of  the  cord  at  a  point  below  the  origin  of  the  phrenic 
nerve,  he  found  that  section  of  the  vagus  was  followed  by  more 
intense  respirations,  and  sometimes  by  a  prolonged  inspiratory 
tetanus,  interrupted  only  by  passive  expirations,  which  became 
more  and  more  frequent,  and  irregular  in  their  rhythm  and  ampli- 
tude. Under  these  conditions  the  excitation  of  the  central  end 
of  the  vagus  had  a  constant  inhibitory  effect,  reducing  the  depth 
of  the  inspiratory  act,  and  the  frequency  of  respiration  may 
be  augmented  or  diminished  according  to  the  more  or  less  pro- 
nounced tetanic  character  of  the  respiration  after  section  of  the 
vagus. 

VII.  Besides  the  pulmonary  fibres  of  the  vagus,  other  influences 
may  affect  the  rhythmical  impulses  of  the  bulbar  respiratory, 
centres.  These  may  emanate  from  the  cerebral  centres,  or  from 
the  periphery  of  the  centripetal  nerves  in  general,  and  particularly 
of  the  sensory  nerves,  with  which  the  mucosa  of  the  nasal, 
buccal,  pharyngeal,  laryngeal  and  tracheal  air-passages  are 
provided. 

The  afferent  influences  from  the  cerebral  centres  to  the  bulbar 
centres  of  respiration  are  conspicuous  after  section  of  the  vagi. 
The  respiratory  type,  which,  as  wre  have  seen  (Fig.  211),  follows 
immediately  on  this  operation,  depends  on  and  is  specially 
maintained  by  the  active  intervention  of  the  cerebral  centres,  in 
lieu  of  the  missing  regulatory  influence  of  the  vagi.  To  prove 
this,  it  is  only  necessary  to  compare  the  effects  of  separation  of 
brain  from  bulb  in  animals  with  intact  and  with  divided  vagi. 
In  the  former,  as  we  know,  the  normal  respiratory  type  is  not 
greatly  modified  after  a  transitory  disturbance  due  to  the  traumatic 
effects  of  the  operation;  in  the  latter,  on  the  contrary,  extraordinary 
changes  in  the  mode  of  respiration  ensue.  The  respiratory  move- 


464  PHYSIOLOGY  CHAP. 

ments  succeed  each  other  with  marked  retardation;  the  inspirations 
become  deeper  and  are  followed  by  long  pauses  (inspiratory 
tetanus) ;  the  expirations  are  rapid,  with  active  intervention  of 
the  abdominal  muscles,  and  are  followed  by  brief  pauses ;  at  the 
same  time  the  normal  rhythm,  i.e.  the  regular  succession  of 
inspirations  and  expirations,  remains  unaltered.  These  effects 
may  vary  in  intensity,  and  inspiratory  tetanus  is  sometimes 
absent,  in  accordance  probably  with  the  varying  degree  of 
operative  traumatism  and  consequent  haemorrhage.  But  in  all 
cases  the  amplitude  of  respiration  or  pulmonary  ventilation  in  the 
unit  of  time  is  diminished  by  about  one-half,  so  that  the  animal 
no  long  time  after  succumbs  to  asphyxia. 

These  striking  results,  as  disclosed  by  the  researches  of 
Marckwald  in  Kronecker's  laboratory  (1887),  and  confirmed  in 
essentials  by  Loewy  in  Zuntz'  laboratory  (1888),  show  the  great 
importance  assumed  by  the  functions  of  the  centres  and  afferent 
nerve-paths  from  brain  to  spinal  bulb  in  pulmonary  respiration, 
when  the  vagi,  which  normally  regulate  respiratory  rhythm,  are 
cut  off.  While,  however,  the  afferent  vagus  tracts  to-  the  bulbar 
respiratory  centres  are  able  perfectly  to  compensate  the  deficit  in 
the  cerebral  paths,  these  last  are  only  partially  able  to  compensate 
for  the  failure  of  the  vagus.  The  effects  of  double  deficiency  show 
'that  the  whole  of  the  other  afferent  paths  to  the  respiratory  centres 
which  remain  intact,  after  section  of  the  vagi  and  separation  of 
the  brain  from  the  bulb,  are  incapable  of  influencing  the  said 
centres  so  as  to  provide  the  respiratory  movements  essential  for 
adequate  pulmonary  ventilation. 

Among  these  afferent  nerve-paths,  special  mention  must  be 
made  of  the  trigeminus,  to  which  the  nasal  mucosa  owes  its 
sensibility ;  the  superior  and  inferior  laryngeal  branches  of  the 
vagus,  which  contain  the  sensory  fibres  to  the  laryngeal  and 
tracheal  mucosa ;  and  the  glosso-pharyngeal,  which  serves  the 
specific  sensibility  of  the  tongue  and  pharynx.  All  these  paths 
are  in  special  relation  with  the  expiratory  centres,  and  their 
stimulation,  whether  at  the  peripheral  ending  or  along  their 
course,  almost  invariably  produces  expiratory  effects. 

We  know  how  readily  sneezing  is  induced  by  chemical  excita- 
tion of  the  nasal  mucosa.  Its  electrical  stimulation  produces 
expiratory  arrest  (Hering  and  Kratschmer).  Expiratory  standstill, 
or  a  true  expiratory  tetanus,  can  also  be  elicited  by  stimulation  of 
the  endings  of  the  trigeminus,  which  are  distributed  to  the  skin  of 
the  face,  if  a  large  surface  is  excited,  e.g.  if  the  animal's  head  is 
dipped  into  water. 

Coughing  is  produced  by  the  stimulus  of  foreign  bodies  upon 
the  mucosa  of  the  larynx  and  windpipe,  transmitted  more 
particularly  by  the  afferent  paths  of  the  superior  and  inferior 
laryngeals.  Gentle  electrical  stimulation  of  the  superior  laryngeal 


xin  RESPIRATORY  RHYTHM  465 

produces  a  retarded  respiration,  with  prolonged  expiratory  pauses. 
With  a  stronger  stimulus  the  expirations  become  very  vigorous, 
and  assume  the  form  of  expiratory  tetanus  (Rosenthal). 

The  effects  of  stimulating  the  glosso  -  pharyngeal  are  less 
constant.  Apparently  this  determines  respiratory  standstill  in 
the  phase  of  the  respiration  that  obtained  prior  to  excitation. 
Few  experiments,  however,  have  been  made  on  this  point. 

In  any  case  these  afferent  nerve  fibres,  situated  along  the 
air-passages,  which  when  stimulated  have  a  moderating  action 
on  the  respiratory  processes,  or  a  decisively  active  expiratory 
influence,  do  not  function  under  ordinary  conditions  of  lite,  since. 
they  have  normally  no  tonicity,  and  are  not  therefore  capable, 
like  the  pulmonary  fibres  of  the  vagus,  of  exerting  a  constant 
influence  upon  the  bulbar  centres.  Cocainisation  of  the  nasal 
mucosa  (Marckwald),  and  bilateral  intracranial  section  of  the 
trigeminus  (Loewy),  effect  no  permanent  alteration  in  respiratory 
rhythm.  On  a  rabbit  operated  on  in  this  way  successive  vagotomy 
produces  no  more  pronounced  effect  than  when  the  operation  is 
performed  on  an  intact  rabbit.  The  paths  of  the  trigeminus  do 
not,  therefore,  normally  exert  any  regulatory  control  upon  the 
respiratory  impulses  sent  out  from  the  centres. 

The  same  may  be  affirmed  of  the  afferent  paths  of  the  glosso-^ 
pharyngeal  and  superior  and  inferior  laryngeals,  section  of  which 
produces  no  permanent  modification  of  respiratory  rhythm. 

All  other  centripetal  paths,  which  lead  directly  or  indirectly, 
from  above  or  from  below,  to  the  respiratory  centres,  and  which 
under  normal  conditions  do  not  influence  the  respiratory  mechanism, 
may,  when  artificially  excited,  or  under  certain  fortuitous  conditions, 
produce  modifications  in  respiration. 

Stimulation  of  the  olfactory  nerve  by  odoriferous  substances 
may  give  rise  now  to  inspiratory  and  now  to  expiratory  effects, 
according  to  the  acuteness  of  the  sensations  evoked,  and  their 
pleasant  or  unpleasant  character.  Electrical  excitation  of  the 
optic  and  auditory  nerves  regularly  produces  acceleration  of 
rhythm,  with  reinforcement  of  inspirations.  The  sensory 
nerves  to  the  skin,  when  slightly  stimulated,  excite  inspiratory 
effects ;  with  painful  stimulation,  they  exaggerate  and  prolong  the 
expiratory  acts.  The  phrenic  nerves  also  contain  afferent  fibres, 
which  when  excited  behave  like  the  cutaneous  nerves.  So,  too,  the 
centripetal  nerves  of  the  sympathetic  system  are  able  reflexly  to 
modify  respiratory  rhythm.  According  to  Pflliger,  excitation  of 
the  splanchnic  invariably  produces  respiratory  effects,  which  do  not 
occur  on  exciting  other  rami  of  the  sympathetic. 

The  majority  of  these  reflexes  are  of  no  essential  importance 
to  the  theory  of  the  nervous  mechanisms  that  normally  and 
continuously  regulate  the  respiratory  rhythm.  On  the  other 
hand,  a  special  importance  in  the  auto-regulation  of  respirations 

VOL.  I  2  H 


466  PHYSIOLOGY  CHAP. 

attaches  to  another  group  of  reflexes,  which  till  now  have  been 
little  considered  by  physiologists,  i.e.  those  reflexes  determined  by 
the  impulses  which  originate  in  the  afferent  nerves  to  the 
respiratory  muscles. 

In  speaking  of  concomitant  respiratory  movements  (p.  421) 
we  said  that  in  many  animals  each  inspiratory  act  is  accompanied 
by  active  dilatation  of'  the  glottis  and  nostrils,  while  constriction 
of  these  apertures  accompanies  each  act  of  expiration.  K.  du 
Bois  -  Keyniond  and  Katzenstein  (1901)  observed  in  dogs  that 
these  movements  of  the  glottis  may  appear  also  in  double  pneumo- 
thorax,  or  when  the  lungs  are  retracted.  Under  these  conditions 
they  noted  that  the  passive  compression  of  the  thorax  (expiratory 
position)  determined  a  constriction,  while  the  elastic  return  to  the 
inspiratory  position  determined  active  dilatation  of  the  glottis. 
From  this  they  inferred  that  these  effects  depend  on  changes  in 
the  position  of  the  thorax  In  all  probability  this  is  an  example 
of  co-ordination  of  reflexes  by  way  of  the  sensory  muscular  and 
tendinous  innervation,  which,  as  we  shall  see  in  Vol.  III.,  has  been 
worked  out  by  Sherrington  for  locomotor  movements.  • 

The  two  authors  named  above  have  indicated  another  fact  of 
great  importance  to  the  theory  of  central  respiratory  innervation. 

/They  described  the  concomitant  respiratory  movements  of  the 
vocal  cords  with  intact  thorax,  during  the  movements  of  the 
diaphragm  determined  by  excitation  of  the  phrenic  in  the  neck. 
Under  these  conditions  they  saw  that  the  tetanic  stimulation  of 
one  or  both  phrenics  determined  movements  of  adduction  in  the 
vocal  cords.  The  contraction  of  the  diaphragm  preceded  by  an 
^'appreciable  interval  the  closure  of  the  glottis,  which  lasted  as 
long  as  the  stimulation  of  the  phrenic.  They  interpreted  these 
reflexes  as  due  to  excitation  of  the  pulmonary  flbres  of  the  vagus, 
which  tallies  with  the  auto -regulatory  theory  of  Hering  and 
Breuer. 

Mislawsky  (1892)  also  communicated  to  the  International 
Physiological  Congress  at  Turin,  a  reflex  action  of  quite  similar 
character,  as  established  by  the  work  of  his  pupil  Luria.  Excita- 
,  tion  of  the  tendinous  centre  of  the  diaphragm  determines  expira- 
tory arrest  of  the  thorax.  Stimulation  of  the  peripheral  trunk  of 
the  phrenic  nerve  has  the  same  effect.  Here,  again,  as  in  the 
case  of  E.  du  Bois  -  Eeymond  and  Katzenstein,  we  have  an 
inspiratory  act  (contraction  of  the  diaphragm)  determining 
reflexly  an  expiratory  act  (adduction  and  closure  of  the  vocal, 
cords,  expiratory  position  of  thorax).  Mislawsky,  too,  holds  that 
^  j  these  reflexes  are  completed  by  way  of  the  pulmonary  vagi.  «  As  a 
matter  of  fact  they  disappear  after  section  of  the  vagi. 

Baglioni  (1903)  in  his  study  of  the  same  reflexes  took  into 
consideration  the  afferent  nerve  paths,  which,  as  we  have  seen,  run 
in  the  phrenic  nerves  along  with  the  afferent  fibres. 


xiii  KESPIKATOKY  EHYTHM  467 

In  order  to  study  the  reciprocal  and  opposite  action  of  the 
two  respiratory  phases  (inspiration  and  expiration)  he  uses  a  pro- 
longed contraction  of  the  rabbit's  diaphragm,  produced  by  direct 
faradisation  of  the  diaphragm  itself,  exposed  by  means  of  a  large 
aperture  in  the  thorax,  artificial  respiration  being  temporarily 
suspended. 

He  noted  that  when  the  contraction  of  the  diaphragm  had 
hardly  begun  the  nostrils  became  fully  dilated,  as  in  every  normal 
act  of  inspiration.  Almost  at  once,  however,  if  the  tetanic  con- 
traction of  the  diaphragm  was  kept  up,  the  nostrils  became  con- 
stricted nearly  to  complete  closure,  and  remained  in  that  position 
during  the  whole  period  of  the  contraction. 

On  bilateral  section  of  the  phrenic  in  the  neck  this  reflex 
disappeared  completely.  Accordingly  it  originates  in  the  con- 
tracted diaphragm,  and  determines  secondarily  the  closure  of  the 
nostrils,  which,  as  we  have  seen  above,  is  a  purely  expiratory  act. 
"  Hence,"  concludes  Baglioni,  "  we  have  here  a  respiratory  reflex  of 
essentially  the  same  character  as  those  respiratory  reflexes  on 
which  Hering  and  Breuer  based  their  theory  of  auto-regulation, 
but  with  this  difference,  that  here  the  afferent  impulse  travels  not 
by  the  pulmonary  vagus  but  by  the  centripetal  fibres  of  the 
phrenic." 

Recently  (1907)  Baglioni  has  emphasised  the  importance  he 
attaches  to  these  respiratory  reflexes,  which  must  be  determined 
by  the  two  respiratory  phases,  the  inspiratory  muscles  by  their 
contraction  exciting  the  centres,  and  thus  reflexly  determining  the 
contraction  of  the  expiratory  muscles,  and  vice  versa. 

VIII.  From  all  that  has  been  said  above,  we  may  deduce  the 
following  conclusions,  which  are  of  fundamental  importance  to  the 
theory  of  respiratory  innervation  : — 

(a)  Normal  respiratory  rhythm  (eupnoecC),  which  is  the  best 
adapted  to  produce  with  minimum  expenditure  of  energy  that 
degree  of  pulmonary  ventilation  which  sutiices  for  the  chemical 
needs  of  the  organism,  is  essentially  conditioned  by  the  activity  of 
the  centripetal  fibres  of  the  pulmonary  branches  of  the  vagus, 
which  are  in  direct  relation  with  the  bulbar  centres.  It  persists 
after  the  separation  of  the  spinal  bulb  from  the  brain. 

(&)  It  is  the  function  of  the  pulmonary  fibres  of  the  vagus  to 
maintain  the  lungs  in  that  state  of  average  dilatation  which 
obtains  when  all  the  respiratory  muscles  are  inactive.  They  are 
excited  on  the  one  hand  by  the  rise  of  pulmonary  pressure  and  p£ 
the  inspiratory  dilatation  of  the  lungs,  which  reflexly  determine 
the  act  of  expiration,  just  as  the  fall  0f  pulmonary  pressure  and 
the  expiratory  retraction  of  the  lungs  reflexly  determine  the  act 
of  inspiration. 

(c)  When  the  auto-regulation  of  respiration  by  means  of  the 
vagi  is. suppressed,  an  abnormal  type  of  respiratory  rhythm  appears, 


468  PHYSIOLOGY  CHAP. 

which,  although  it  provides  for  a  degree  of  pulmonary  ventilation 
sufficient  to  maintain  life,  must  yet  be  termed  dyspnoeic,  since  it 
is  not  obtained  without  useless  expenditure  of  muscular  energy. 
Under  these  conditions  it  seems  to  us  probable  that  a  vicarious 
self -regulation  comes  into  play,  due  to  the  rhythmical  and 
alternate  excitation  of  the  sensory  paths  to  the  inspiratory  and 
expiratory  muscles. 

(d)  The  dyspnoeic  respiration,  consequent  on  section  of  the  vagi, 
is  largely  maintained  by  the  active  intervention  of  the  cerebral 
respiratory  centres  which  tend  to  compensate  the  deficiency  of  the 
vagus.     When,  indeed,  the  influence  of  the  descending  cerebral 
tracts    is    also    cut    off,   respiration    becomes    far    more    highly 
dyspnoeic,  and  is  inadequate  for  the  needs  of  existence,  although 
rhythm,  i.e.  the  alternation  of  inspiratory  and  expiratory  acts,  still 
persists. 

(e)  All  the  other  centripetal   nerves,  which   are   capable   of 
reflexly   influencing    the    respiratory   mechanism,   are    normally 
inactive,  since   their  occlusion  produces  no  apparent  change   in 
respiration,  and  they  are  inadequate,  after  the  vagi  a'nd  afferent 
cerebral  paths  to  the  bulb  have  been  cut  out,  to  compensate  the 
deficiency  and  substitute  their  own  functions. 

It  would  be  a  mistake  to  conclude  from  these  facts  as  a  whole 
that  the  rhythmically  alternating  impulses  which  emanate  from 
the  inspiratory  and  expiratory  centres  localised  in  the  spinal  bulb 
are  merely  reflex  acts  determined  by  stimulation  of  the  said 
afferent  nerve  tracts.  As  a  matter  of  fact,  we  have  seen  that 
respiratory  rhythm,  even  when  the  spinal  bulb  is  cut  off  from  the 
brain  and  section  of  the  vagi,  persists  in  a  highly  energetic  form, 
although  it  is  inadequate  for  physiological  requirements.  If,  after 
these  two  operations,  we  proceed  to  a  third,  in  which  the  cervical 
cord  is  bisected  at  the  level  of  the  exit  of  the  fourth  pair  of 
cervical  nerves,  from  which  the  fibres'  of  the  phrenic  emerge,  the 
thoracic  abdominal  respiratory  rhythm  persists,  though  it  is 
represented  almost  exclusively  by  the  energetic  rhythmical  con- 
tractions of  the  diaphragm  (Eosenthal).  Lastly,  if  the  spinal  bulb 
is  suddenly  and  completely  isolated  by  another  transverse  cut 
below  the  tip  of  the  calamus  scriptorius  all  thoracic  movement 
ceases,  but  the  facial,  nasal,  and  laryngeal  movements  that 
accompany  the  movements  of  respiration  continue.  That  is  to 
say,  the  respiratory  centres  persist  in  their  rhythmical  functions, 
although  these  can  only  find  expression  in  the  few  motor  paths 
that  remain  (Eosenthal),  . 

Since,  however,  we  know  that  the  sensory  tracts  whicn  are 
still  connected  with  the  bulb  under  these  conditions  of  isolation 
are  able  reflexly  to  provoke  rhythmic  and  alternate  excitation,  it 
would  be  rash  to  conclude  from  these  data  that  the  respiratory 
rhythm  of  the  bulbar  centres  is  automatic  in  character,  i.e.  entirely 


xin  RESPIRATORY  RHYTHM  469 

independent  of  external  stimuli.  It  is  also  legitimate  to  suspect 
that  the  rhythmical  activity  of  the  isolated  bulb  may  be  main- 
tained by  irritation  from,  the  sections  and  the  external  agents 
acting  on  the  surface  of  these  sections.  We  must  now  turn  to  a 
striking  series  of  facts  which  show  that  the  rhythmical  activity  of 
the  respiratory  centres  is  influenced  in  great  measure,  besides  the 
afferent  stimuli  by  the  nerve  paths,  by  the  condition  of  the  blood 
and  lymph  that  are  circulating  in  them,  i.e.  by  the  nature  of  the 
medium  which  bathes  the  nervous  elements  of  which  they  are 
constituted. 

IX.  Under  all  the  varied  circumstances,  natural  or  experi- 
mental, in  which  there  is  an  abnormal  rise  of  venosity  of  the 
blood  in  consequence  of  the  diminished  gaseous  exchanges  between 
the  environment  and  the  organism,  dyspnoea  is  produced,  i.e. 
increased  intensity  and  frequency  of  the  respiratory  rhythm. 
This  occurs  regularly  : 

(a)  When  the  animal  (or  man)  is  forced  to  breathe  an  atmo- 
sphere surcharged  with  carbonic  acid  ; 

(&)  Or  an  atmosphere  poor  in  oxygen  and  rich  in  indifferent 


(c)  When  under  any  morbid  conditions  (pneumonia,  pleuritic 
effusions,    pneumothorax)    the    alveolar    respiratory    surface    is 
abnormally  diminished ; 

(d)  When  owing  to  uncompensated  organic  lesions  of  the  heart 
there  is  an  abnormal  retardation  of  circulation  ; 

(e)  When,   lastly,  owing  to  profuse  haemorrhage,  or  copious 
bleeding,  the  mass  of  blood  in  circulation  is  largely  diminished. 

Since  the  respiratory  movements  are  destined  by  the  ventila- 
tion of  the  lung  to  provide  for  the  normal  gas  exchanges  between 
the  atmosphere  and  the  blood,  and  indirectly  between  the  blood 
and  the  tissues,  these  facts  show  that  the  amplitude  of  the 
respiratory  movements,  i.e.  the  degree  of  pulmonary  ventilation, 
increases  with  the  need  for  increased  elimination  of  C02  and  0., 
absorption.  Accordingly,  there  is  a  certain  degree  of  adaptation 
between  the  gas  exchanges  and  the  respiratory  activity,  which 
implies  that  either  the  carbonic  acid,  or  other  waste  products  of 
the  tissues  avid  of  oxygen,  act  as  direct  stimuli  to  the  respiratory 
centres,  or  at  least  modify  their  metabolism  so  as  to  increase  their 
rhythmical  and  alternate  function. 

The  theory  of  adaptation  between  the  need  for  air  and  the 
respiratory  magnitude  of  ventilation  is  confirmed  by  the  fact  that 
there  is  exaggerated  activity  of  the  respiratory  centres,  and  there- 
fore of  the  depth  and  frequency  of  respiration,  whenever  the 
organic  processes  of  combustion,  i.e.  the  consumption  of  oxygen 
and  production  of  carbonic  acid,  are  increased.  The  most  classical 
example  of  this  fact  is,  under  normal  conditions,  the  dyspnoea 
developed  in  consequence  of  intense  muscular  work.  The  influence 


470  PHYSIOLOGY  CHAP. 

exercised  by  work  upon  the  respiration  of  the  muscular  tissues 
and  the  combustion  which  takes  place  within  them  is  enormous. 
To  form  an  idea  of  it  we  must  consider  the  variations  per  tiin6 
unit  of  the  quantity  of  carbonic  acid  given  off  in  different  states 
of  the  muscle.  According  to  Gad,  the  same  individual  gave  off  in 
one  minute  from  the  lungs : — 

During  sleep 0'38  grms.  of  C02 

During  the  waking  state  and  horizontal  position         .  0*57  „ 

In  walking 1-42          „ 

In  more  rapid  walking 2O3  „ 

In  climbing 3'83  „ 

It  will  be  noted  that  in  the  work  of  climbing  ten  times 
as  much  carbonic  acid  is  eliminated  as  in  sleep.  The  need 
of  breathing,  therefore,  increases  proportionately,  and  is  amply 
•satisfied  by  the  dyspnoea  which  provides  for  the  due  elimination  of 
the  excess  C02  formed,  and  absorption  of  the  excess  02  consumed. 

Analysis  of  the  blood  gases  of  animals  which  are  dyspnoeic  in 
consequence  of  muscular  work  show,  however,  that  boj/h  carbonic 
acid  and  oxygen  are  present  there  in  normal  quantities.  Accord- 
ing to  the  elegant  researches  of  Geppert  and  Zimtz  (1888),  the 
oxygen  is  somewhat  increased  and  the  carbonic  acid  considerably 
diminished  below  the  normal.  There  is  thus  a  certain  adaptation 
between  the  need  of  air  and  the  pulmonary  ventilation,  but  it  is 
not  strictly  commensurate  with  the  chemical  requirements  of  our 
tissues.  The  dyspnoea  of  muscular  work  exceeds  the  limit  of  strict 
necessity,  i.e.  there  is  a  superfluous  increase  of  the  respiratory 
activity  which  cannot  be  explained  either  by  the  increase  of  C02, 
or  by  the  diminution  of  02  in  the  blood.  Since  the  effect  of 
energetic  muscular  work  is  to  diminish  the  alkalinity  of  the  blood, 
it  has  been  supposed  (in  order  to  account  for  the  increased  activity 
of  the  respiratory  centres)  that  the  muscles  during  their  activity 
develop  an  acid  product  of  consumption,  different  from  carbonic 
acid,  which  is  capable  of  exciting  the  respiratory  centres  (Curt 
Seehman).  It  is  possible  that  this  product  may  be  lactic  acid, 
which  is  developed  and  poured  out  into  the  blood  by  the  muscles 
during  their  activity  (Spiro),  and  which  is  found,  e.g.,  in  the  urine 
of  soldiers  after  a  long  and  fatiguing  march,  or  gymnastic 
exercises  (Colasanti). 

But  in  explaining  the  superfluous  increase  of  respiratory 
activity  in  the  dyspnoea  of  muscular  fatigue,  we  must  also  take 
into  consideration  the  increased  temperature  of  the  blood,  which 
is  necessarily  associated  with  the  increased  combustion  of  the 
muscular  tissues,  and  which  in  itself  is  capable  of  provoking  a 
dyspnoeic  acceleration  of  respiratory  rhythm  to  which  the  name  of 
tachypnoea,  polypnoea,  or  thermal  dyspnoea,  characterised  by  very 
rapid  and  superficial  respirations,  with  increased  tone  of  the 
inspiratory  centres,  has  been  given. 


xin  EESPIEATOEY  KHYTHM  471 

The  simplest  case  of  tachypnoea  occurs  in  dogs,  under  perfectly 
normal  conditions,  during  the  hottest  days  of  summer.  The 
accelerated  rhythm,  which  causes  an  abundant  evaporation  of 
water,  is,  in  this  case,  a  protection  against  an  abnormal  rise  in 
temperature  of  the  blood,  rather  than  against  the  accumulation  of 
carbonic  acid  there  (Bichet).  The  thermal  excitation  of  the 
cutaneous  nerves  is  probably  in  this  case  the  sole  condition  acting 
reflexly  upon  the  bulbar  centres,  so  as  to  determine  tachypnoea 
(Gad). 

Under  all  other  contingencies  in  which  there  is  already  an 
abnormal  rise  in  the  temperature  of  the  blood,  as  in  fever  due  to 
any  cause,  the  phenomenon  of  dyspnoea  is  much  more  complex ;  but 
one  of  the  fundamental  conditions  that  determines  it  is  certainly 
the  abnormal  rise  of  excitability  in  the  centres,  due  to  the 
heightened  temperature  of  the  blood  that  circulates  in  them. 
Goldstein  demonstrated  this  in  1872  in  Fick's  laboratory.  In 
order  to  avoid  rise  of  general  temperature  in  the  animal,  he 
surrounded  the  carotids  with  two  little  metal  sheaths,  with  double 
walls,  within  which  he  circulated  water  warmed  so  as  to  produce 
febrile  temperature  in  the  pharynx,  while  the  rectal  temperature 
remained  steady.  There  was  at  once  a  rhythmical  acceleration  of 
respiration  (tachypnoea)  in  the  animal,  due  solely  to  the  heating  of 
the  blood  circulating  in  the  head,  which  raised  the  excitability  of 
the  bulbar  centres  (particularly  of  the  inspiratory  centres).  In 
fact,  under  these  conditions  it  was  found  impossible  to  produce 
apnoea  (which  we  shall  discuss  elsewhere)  with  artificial 
respiration. 

In  face  of  these  facts  it  seems  indubitable  that  the  pulmonary 
ventilation,  determined  by  the  dyspnoea  due  to  muscular  fatigue, 
which  is  excessive  as  regards  the  chemical  needs  of  the  tissues, 
may  and  should  be  explained,  at  least  partly,  as  an  effect  of  the 
increased  excitability  of  the  bulb,  consequent  on  increased  tempera- 
ture of  the  blood.  The  genesis  of  febrile  dyspnoea  is  highly 
similar. 

Jappelli  has  recently  (1906),  from  his  experiments  on  man  and 
other  animals  (dog,  rabbit,  pigeon),  demonstrated  a  fact  which 
tends  to  explain  many  forms  of  polypnoea  in  muscular  work 
(running,  jumping,  etc.)  in  a  different  way  to  those  heretofore 
considered,  i.e.  independent  of  the  chemical  or  thermal  changes  in 
the  blood  which  irrigates  the  respiratory  centres.  He  saw  that 
there  is  in  the  respiratory  nerve  centre  a  distinct  tendency  to 
synchronise  its  rhythmical  and  alternate  impulses  with  the 
external  rhythmical  impulses,  which  .are  eventually  transmitted  to 
the  central  nervous  system  via  the  sensory  nerves.  If,  e.g.,  in  a  dog 
breathing  normally,  the  central  end  of  the  sciatic  is  rhythmically 
excited  with  weak  induced  currents  of  varying  frequency  (40-80 
per  minute),  it  will  be  seen  after  a  longer  or  shorter  latent  period 


472  PHYSIOLOGY  CHAP. 

that  the  respiratory  rhythm  is  modified,  becoming  more  frequent 
and  perfectly  synchronous  with  the  rhythm  of  the  artificial  stimuli. 
Again,  the  polypnoea  induced  in  man  by  rhythmical  exercises  which 
impart  considerable  vertical  oscillations  to  the  torso  (running, 
jumping),  is  characterised  by  a  tendency  to  synchronisation 
between  the  respiratory  phases  and  the  rhythm  of  rise  or  fall  of 
the  centre  of  gravity.  These  rhythmical  movements  of  running 
or  jumping  must,  therefore,  determine  afferent  nerve  impulses  to 
whose  rhythm  the  respiratory  centre  tends  to  adjust  the  rhythm 
of  its  own  proper  activity.  And  since  the  rhythm  of  the  afferent 
nerve  impulses  is  in  these  cases  more  frequent  than  the  rhythm  of 
normal  respiration,  dyspnoea  ensues  as  the  direct  effect. 

This  theory  also  explains  certain  peculiarities  of  the  said 
dyspnoea;  for  example,  the  fact  of  its  rapid  onset,  at  the  very 
beginning  of  the  running  and  jumping,  i.e.  before  it  is  possible  to 
assume  any  production  of  toxic  substances  or  rise  of  tempera- 
ture, such  as  are  invoked  in  the  preceding  theories.  So,  too, 
its  immediate  disappearance,  sometimes  at  the  very  moment 
the  exercise  is  over.  On  this  theory,  again,  it  is  easy  to  explain 
the  other  fact  known  to  professional  athletes,  to  wit,  that  properly 
trained  runners  are  able  to  hold  out  for  a  long  time  without 
experiencing  dyspnoea. 

"  We  can  also  understand  "  (adds  Jappelli)  "  what  the  import- 
ance of  learning  how  to  take  breath  in  running  may  be.  How,  if 
this  were  determined  by  the  quantity  of  blood  circulating  in 
the  capillary  network  of  the  bulb  (deficit  of  02,  increase  of  C02), 
could  it  be  modified  by  a  physical  education  ?  The  polypnoea 
of  running  is,  however,  mainly  a  luxus-respiration,  an  effect  of 
synchronisation,  which  represents  a  useless  expenditure  of  energy, 
and  which,  once  the  exigencies  of  the  respiratory  exchanges  are 
satisfied,  may  be  modified  for  the  sake  of  avoiding  fatigue.  The 
education  of  respiratory  rhythm  in  a  runner  therefore  amounts  to 
developing  in  him  an  inhibitory  cerebral  faculty,  so  that  he 
moderates  the  frequency  of  his  respiration,  opposing  the  tendency 
towards  synchronisation  with  the  movements  of  the  lower  limbs." 

X.  Let  us  now  examine  whether  in  normal  quiet  respiration 
(eupnoea)  the  respiratory  activity  is  commensurate  with  the 
quantity  of  oxygen  required  by  the  tissues,  and  the  carbonic  acid 
which  they  exhale ;  or  if  in  this  case  also,  as  in  the  dyspnoea  of 
muscular  work,  the  renewal  of  pulmonary  air  is  in  excess  of  what 
is  required,  the  nervous  mechanisms  of  the  respiratory  rhythm 
being  to  a  certain  extent  independent  of  the  gaseous  content  of 
the  blood  circulating  in  them. 

Kosenthal  in  1862  espoused  the  first  theory  on  the  strength  of 
a  number  of  experiments,  more  particularly  the  phenomenon  of 
experimental  apnoea,  of  which  he  may  be  termed  the  discoverer, 
and  which  we  shall  consider  below.  His  theory,  broadly  speaking, 


xin  KESPIKATORY  EHYTHM  473 

found  general  acceptance,  and  Pflliger  gave  it  the  authority  of  his 
name  in  1868. 

A.  Mosso  was  the  first  who,  in  1885,  pointed  to  some  quite 
evident  facts  which,  according  to  him,  show  that  "  the  number  and 
extent  of  the  respiratory  movements  are  not  always  in  close  relation 
with  the  respiration  of  the  tissues  and  the  blood,  while  they  are 
directly  proportional  with  the  need  for  supply  of  oxygen  or 
elimination  of  carbonic  acid."  He  gave  the  name  of  extra-  or 
luxus-respiration  to  the  excess  renewal  of  air  in  the  lungs,  such 
as  normally  occurs  and  is  not,  strictly  speaking,  necessary  to  the 
organism. 

Some  of  the  facts  which  he  brings  forward  do  not  really 
appear  to  stand  in  close  relation  with  the  theory  of  luxus- 
consumption.  Such,  e.g.,  are  the  well- known  fact  that  respira- 
tion is  profoundly  modified  by  simple  nervous  activity  (emotions, 
intellectual  work)  quite  independent  of  the  degree  of  venosity 
of  the  blood;  that  dogs  after  running  frequently  pass  from 
deep  respiration  (dyspnoea)  to  quick  and  superficial  breathing 
(tachypnoea)  as  if  the  register  were  suddenly  changed  without 
apparent  reason ;  again,  that  in  sleep,  both  in  man  and  other 
animals,  temporary  disturbances  of  a  purely  nervous  character 
may  be  observed  in  the  regularity  of  the  rhythm.  All  these 
effects  confirm  what  we  said  above  as  to  the  influence  exerted  by 
the  nervous  system  upon  the  regulation,  and  more  particularly 
the  mode  of  distribution  of  the  work  of  the  respiratory  muscles, 
and  have  nothing  to  do  with  the  capacity  for  pulmonary  ventila- 
tion, which  may  continue  practically  unchanged  in  the  time-unit 
under  very  dissimilar  and  even  opposite  forms  of  respiratory 
rhythm  (Kosenthal). 

Another  fact  brought  forward  by  Mosso  is  more  significant, 
i.e.  that  we  can  voluntarily  reduce  to  about  one-half  the  amount 
of  air  inspired,  without  inconvenience,  for  a  considerable  period 
(10-15  minutes).  At  the  same  time  this  would  only  bear  on  the 
theory  of  luxus-respiration,  if  it  could  be  proved  that  breathing, 
when  voluntarily  restrained  for  so  long  a  time,  would  not  be 
followed  by  a  compensatory  dyspnoea. 

Lastly,  we  attach  great  importance  to  the  observations  made 
by  Mosso  during  his  Alpine  excursions,  which  show  that  at  a  level 
of  3000  metres  much  less  air  is  breathed .  than  at  sea-level : 
hence  at  sea-level  the  amount  of  air  respired  far  exceeds  the  needs 
of  the  organism.  In  proportion  as  one  ascends,  the  superfluous  or 
luxus-respiration  diminishes  owing  to  the  rarefaction  of  the  air. 
These  high  altitude  effects  do  not,  however,  appear  to  be  constant, 
which  as  we  shall  see  impairs  their  cogency  for  luxus-respiration 
in  the  plains. 

According  to  Mosso,  luxus-respiration  (which  we  may  shortly 
designate  eupnoea)  is  profitable  to  the  organism,  because  it  makes 


474  PHYSIOLOGY  CHAP. 

the  regulating  factors  less  complex.  It  is  clear  that  if  the 
ordinary  respiratory  mechanism  were  not,  within  certain  limits, 
independent  of  the  chemical  needs  of  the  body,  or  the  gas  content^ 
of  the  blood,  then  "  at  every  change  of  the  barometer  (some  of 
which  are  enormous)  every  man  and  every  animal  would  have 
suddenly  to  alter  both  frequency  and  depth  of  respiration,  in  order 
to  equalise  the  changes  in  the  atmosphere  "  (Mosso,  1898). 

Here,  however,  we  touch  upon  new  problems,  which  demand 
solution.  For  if  we  accept  this  theory  of  eupnoea,  it  may  be 
asked :  "  What  are  the  external  factors  causing  this  excess  of 
pulmonary  ventilation  ?  If  in  the  dyspnoea  from  hard  muscular 
work,  pulmonary  ventilation  increases  to  oppose  the  increased 
venosity  of  the  blood,  and  if  this  effect  exceeds  the  immediate 
requirement,  must  not  the  same  effect  occur  in  eupnoea,  and  the 
venosity  of  the  blood  diminish  to  such  an  extent  that  it  would  in 
a  short  time  become  inadequate  to  maintain  the  activity  of  the 
centres  ?  If,  in  order  to  explain  the  dyspnoea  of  work,  we  are 
obliged  to  invoke  the  presence  of  a  (probably  acid)  waste  product  of 
muscle  in  the  blood,  capable  of  sur-exciting  the  respiratory  centres, 
are  we  not  equally  obliged  to  admit  that  an  analogous  product 
may  be  acting  in  eupnoea,  stimulating  the  activity  of  the  centres, 
and  raising  the  respiratory  capacity  (by  about  one-half)  beyond 
the  immediate  need  ? 

Again,  how  does  the  chemistry  of  respiration  alter  at  high 
altitudes  where  luxus-respiration  ceases  ? 

According  to  the  analyses  of  blood  gases  made  on  the  dog  by 
Friinkel  and  Geppert  (1833)  to  test  the  effect  of  varying  baro- 
metric pressures,  in  air  rarefied  to  a  pressure  of  410  mm.  the  02  and 
(J02  content  of  arterial  blood  is  not  perceptibly  altered ;  and  at  a 
pressure  of  198  mm.  the  loss  of  gases  from  the  blood  is  still  extremely 
small  (1  part  0.2  and  T65  part  C02).  Mosso  attributes  great 
importance  to  this  relatively  minute  diminution  of  the  C02  of  the 
blood.  He  believes  it  to  represent  a  state  of  the  blood  contrary  to 
that  which  prevails  in  asphyxia,  and  proposes  to  call  it  acapnia, 
holding  it  to  be  one  of  the  causes  of  mountain  sickness.  This 
conclusion  seems  to  us  to  be  premature  and  hazardous.  We  admit 
that  acapnia,  or  the  abnormal  diminution  of  C0.7  in  the  blood,  can 
only  be  regarded  as  the  effect  of  two  opposite  processes,  either,  i.e., 
of  a  diminished  production  of  C09,  as  in  sleep,  or  of  its  augmented 
excretion,  as  in  artificial  or  forced  voluntary  respiration.  Now 
neither  the  one  nor  the  other  condition  of  acapnia  is  fulfilled 
in  respiration  at  a  high  altitude  above  sea-level.  From  the 
experiments  undertaken  by  Mosso  upon  three  soldiers,  after  they 
had  rested,  so  as  to  exclude  the  effects  of  muscular  fatigue,  it 
appeared  that  "  no  important  modification  in  the  elimination  of 
CO2  and  the  volume  of  respired  air  can  be  detected  at  high 
altitudes."  This  proves  that  even  in  rarefied  air  "  the  organism 


xiii  EESPIEATOEY  EHYTHM  475 

requires  its  normal  supply  of  oxygen,"  i.e.  it  consumes  the  same 
amount,  and  therefore  eliminates  the  same  quantity  of  carbonic 
acid.  It  may  be  noted  in  passing  that  these  facts  contradict 
the  preceding  data  on  which  Mosso  rests  his  theory  of  luxus- 
respiration. 

Eecently  (1906)  Zuntz,  Loewy,  F.  Miiller,  and  Caspari,  in  the 
course  of  their  numerous  researches  on  the  physiological  action 
of  climate  at  high  altitudes  and  of  alpine  excursions  on  man, 
have  enumerated  a  series  of  observations  and  data  which  directly 
contradict  the  theory  of  acapnia.  They  found,  as  a  matter  of  fact, 
that  there  is  in  the  majority  of  cases  a  progressive  diminution 
of  C02  tension  in  the  lungs  in  proportion  with  the  altitude.  Thus, 
e.g.,  while  the  tension  of  the  pulmonary  C09  was  in  Zuntz,  at  a 
barometric  pressure  of  715  mm.,  38*5  mm.,  at  a  barometric 
pressure  of  689'9  mm.  it  fell  to  32'6,  becoming  27'2  at  439'3  mm. 
barometric  pressure.  It  is,  however,  true  that  there  is  a 
simultaneous  increase  of  respiratory  intensity,  i.e.  an  augmentation 
of  pulmonary  ventilation. 

The  diminished  pulmonary  tension  of  the  C0.2  would  thus  be  a 
secondary  effect  of  increased  ventilation,  which  in  its  turn  depends 
upon  the  diminution  of  the  oxygen  in  the  respired  air. 

They  further  note  that  not  every  individual  presents  the  same 
diminution  of  COQ  tension  in  respect  of  altitude.  In  one  person, 
e.g.,  no  diminution  in  C02  tension  was  noted,  and  yet  he  was  one 
of  those  who  suffered  most  from  mountain  sickness.  Others,  on 
the  contrary,  who  exhibited  the  said  diminution,  were  exempt 
from  sickness. 

In  order,  at  least  to  some  extent,  to  clear  up  this  uncer- 
tainty as  tro  the  theory  of  eupnoea,  and  the  better  to  define  the 
nature  of  the  relations  existing  between  the  chemistry  and  the 
mechanics  of  respiration,  i.e.  between  the  gas  content  of  the  blood 
and  the  capacity  of  pulmonary  ventilation,  it  will  be  well  diligently 
to  examine  the  various  conditions  under  which  it  is  possible  to 
observe  the  phenomenon  of  apnoea. 

XI.  If  the  rhythmic  and  alternate  activity  of  the  respiratory 
centres  is  strictly  bound  up  with  the  quantity  of  oxygen  and 
carbonic  acid  of  the  blood  that  is  circulating  through  them,  it 
should  be  suspended  when  the  venosity  of  the  blood  is  artificially 
reduced,  so  as  to  render  pulmonary  ventilation  useless.  The  name 
of  apnoea  has  been  given  to  such  suspension  of  the  respiratory 
movements  when  they  have  become  temporarily  superfluous. 

Hook  (1667)  (see  p.  371)  was  the  first  to  observe  it,  but  he 
formulated  no  conclusion  as  regards  the  process  by  which  the 
respiratory  centres  enter  into  rhythmic  activity.  The  first  to 
study  apnoea  by  making  it  the  basis  of  the  doctrine  of  respiratory 
rhythm  was,  as  we  have  stated,  Eosenthal  (1862).  His  work  was 
taken  up  and  enlarged  by  Pfliiger  (1868). 


476  PHYSIOLOGY  CHAP. 

We  have  seen  that  when  artificial  respiration  with  the  bellows 
is  performed  on  any  animal,  the  lungs  being  rhythmically  dilated 
in  proportion  as  the  normal  limits  are  transcended,  the  animal, 
owing  to  the  auto-regulation  set  up  by  the  vagus,  reacts  to  each 
insufflation  by  a  respiratory  movement.  After  a  few  insufflations, 
however,  these  reactions  diminish,  and  soon  cease  altogether.  If 
artificial  respiration  is  now  suspended,  the  animal  remains  for  a 
few  seconds,  half  a  minute  at  the  outside,  without  breathing,  it 
has  become  apnoeic.  To  Rosen  thai  this  phenomenon  of  apnoea 
appeared  to  be  an  experiment-urn  crucis  in  favour  of  the  doctrine 
which  subordinates  the  respiratory  movements  to  the  degree  of 
venosity  of  the  blood.  When  there  is  a  relative  augmentation  of 
C02,  and  a  relative  diminution  of  O2,  there  is  in  the  time  unit 
a  corresponding  augmentation  in  the  respiratory  capacity.  The 
latter  then  depends  upon,  and  is  in  strict  ratio  with,  the  venosity 
of  the  blood.  The  vagi,  according  to  Eosenthal,  only  distribute 
the  work  of  the  respiratory  muscles  in  various  ways,  since  it 
remains  approximately  the  same  after  section  of  these  nerves. 

But  the  forced  apnoea  of  artificial  respiration  is  by  no  means 
so  simple  a  phenomenon  as  was  assumed  by  Rosenthal ;  indeed 
it  is  highly  complex.  It  can  be  easily  demonstrated  that  it 
depends  not  so  much  on  the  diminished  venosity  of  the  blood,  as 
on  an  inhibition  or  reflex  paralysis  of  the  rhythmical  activity  of 
the  centres,  determined  by  mechanical  excitation  of  the  centripetal 
pulmonary  branches  of  the  vagi.  Brown -Sequard  (1877)  was  the 
first  who  brought  forward  this  opinion,  founding  it  on  the  fact 
(subsequently  confirmed  by  all  experimenters)  that  apnoea  is 
entirely  absent  or  lasts  for  a  few  seconds  only,  when  forced 
respiration  is  employed  after  section  of  the  vagi.  It  is  therefore 
conditional  on  the  integrity  of  those  nerves. 

On  the  other  hand,  there  are  not  wanting  facts  which  show 
that  the  diminished  venosity  of  the  blood  is  of  secondary  importance 
in  determining  apnoea.  In  1865  Thiry  noticed  that  he  was  able  to 
produce  apnoea  even  when  air  mixed  with  half  its  bulk  of  some 
indifferent  gas,  such  as  hydrogen,  was  insufflated.  It  was  sub- 
sequently found  by  Fredericq,  Gad,  and  Knoll  that  in  order  to 
produce  apnoea,  it  is  not  necessary  to  insufflate  with  pure  air,  but 
that  provided  the  vagi  are  intact,  repeated  insufflation  with  the 
same  air  (which  becomes  more  and  more  charged  with  carbonic  acid 
and  poorer  and  poorer  in  oxygen)  suffices  to  produce  the  phenomenon. 
Knoll  further  observed  that  after  prolonged  pulmonary  ventilation, 
the  apnoeic  state  is  persistent  even  when  the  blood  becomes  blackish, 
i.e.,  has  assumed  the  character  of  asphyxial  blood.  On  exposing 
the  heart  in  a  rabbit,  by  removal  of  the  sternum,  without  opening 
the  pleura  (which  is  possible  in  this  animal  owing  to  the  persist- 
ence and  bulk  of  the  thymus)  and  inducing  apnoea  by  energetic 
artificial  respiration,  Gad  observed  that  the  right  auricle  preserves 


xiii  KESPIEATOEY  EHYTHM  477 

the  usual  venous  colour,  while  the  left  auricle  is  at  first  of  a  bright 
arterial  scarlet,  and  then  grows  darker  during  the  course  of  the 
apnoea,  a  process  which  usually  ceases  only  when  the  colour  of  the 
left  auricle  has  become  much  darker  than  the  normal.  This  shows 
that  the  mechanical  action  of  artificial  respiration  with  the  bellows 
causes  by  means  of  the  vagi  a  diminution  of  excitability  in  the 
respiratory  centres.  In  fact  a  highly  venous  blood,  which  under 
normal  conditions  would  determine  a  rise  of  excitability  in  the 
rhythmical  activity  of  the  centres,  is  unable,  after  vigorous  artificial 
respiration,  to  interrupt  the  apnoea. 

From  these  facts  as  a  whole  we  may  conclude  that  the  apnoea 
obtained  with  artificial  respiration  is  the  result  of  a  certain  ratio 
between  the  venosity  of  the  blood  and  the  excitability  of  the 
respiratory  centres.  Since  it  is  thus  possible  to  obtain  apnoea  even 
when  the  venosity  of  the  blood,  far  from  being  reduced,  has 
exceeded  the  normal  limits  :  since,  on  the  other  hand,  it  does  not 
appear  after  section  of  the  vagi,  i.e.,  when  the  moderating  influence 
exerted  by  these  nerves  upon  the  excitability  of  the  bulbar  centres 
when  mechanically  stimulated,  is  eliminated, — it  follows  that  the 
said  apnoea  must  depend  principally  upon  the  reduced  excitability 
of  the  respiratory  centres. 

Miescher  proposes  to  give  the  name  of  true  apnoea  to  that  which 
is  determined  by  the  diminished  venosity  of  the  blood,  and  spurious 
apnoea  to  that  which  depends  on  the  diminished  excitability  of  the 
respiratory  centres.  Before  accepting"  this  distinction,  we  must 
inquire  whether  there  is  any  true  apnoea  in  Miescher's  sense,  and 
whether  it  is  possible  to  produce  it  artificially  in  man  or  other 
animals. 

XII.  Let  us  in  the  first  place  consider  the  phenomenon  of 
foetal  apnoea.  We  know  that  under  normal  conditions,  so  long  as  it 
is  contained  within  the  uterus,  the  foetus  performs  no  respiratory 
movements  ;  it  is  apnoeic.  The  placental  circulation  provides  for 
the  exchange  of  gases  necessary  to  the  internal  respiration  of  the 
foetal  tissues.  The  umbilical  arteries  conduct  the  blood  that  has 
become  venous  in  these  tissues  to  the  placenta,  and  the  umbilical 
veins  reconduct  the  blood  which  has  become  arterial  by  gas 
exchanges  with  the  maternal  blood,  to  the  foetus.  The  trans- 
formation of  arterial  into  venous  blood  is,  however,  but  little 
accentuated  in  the  foetus.  According  to  Zweifel  and  Zuntz,  the 
colour  of  the  blood  in  the  umbilical  arteries  differs  little  from  that 
of  the  umbilical  veins,  showing  that  the  foetus  consumes  little 
oxygen,  and  gives  off  little  carbonic  acid.  Enclosed  within  the 
maternal  womb,  immersed  in  a  tepid  bath,  it  has  no  need  to 
provide  for  its  own  calorification ;  the  muscles  and  digestive 
glands  are  in  almost  complete  repose ;  the  heart  is  the  only 
foetal  organ  that  functions  with  any  activity,  and  consumes  a 
certain  amount  of  energy  (Pfliiger).  At  the  seventh  month  the 


478  PHYSIOLOGY  CHAP. 

foetus  is  perfectly  vitalised,  so  that  its  respiratory  apparatus  is 
even  at  that  time  fully  developed  and  ready  to  function.  If,  then, 
during  the  last  two  months  of  pregnancy  no  respiratory  acts  ar»3 
performed  under  normal  conditions,  we  may  say  that  it  is  in  a 
state  of  apnoea,  because  having  every  aptitude  for  breathing,  it 
does  not  breathe. 

At  the  end  of  1858  Schwarz  enunciated  the  doctrine  that 
foetal  apnoea  depends  on  the  fact  of  the  apnoeicity  of  foetal  blood 
in  relation  to  the  low  excitability  of  the  respiratory  centres.  The 
foetus  does  not  breathe,  because  the  physiological  cravings  of 
its  tissues  are  amply  provided  for  by  the  utero-placental  gas 
exchanges,  but  we  must  also  admit  that  the  excitability  of  its 
respiratory  centres  is  lower  than  in  those  of  the  mother,  the 
activity  of  which  is  maintained  by  blood  of  the  same  degree  of 
venosity  as  that  which  circulates  in  the  foetus. 

The  first  respiratory  act  of  the  foetus  is  accomplished  when  any 
cause  whatsoever  compresses  the  vessels  of  the  umbilical  cord,  or 
impedes  access  of  the  maternal  arterial  blood  by  the  placenta. 
This  may  occur  even  within  the  uterus,  as  Vesalius  pointed  out  in 
1542.  Under  these  conditions,  if  the  interruption  to  the  gas 
exchange  persists,  the  foetus  may  perish,  asphyxiated  within  the 
uterus.  But  if  the  venosity  of  the  foetal  blood  develops  slowly, 
as  when  the  mother  is  slowly  dying,  the  foetal  respiratory  centres 
gradually  lose  their  excitability  before  ever  they  have  become  active. 

Under  normal  conditions  the  foetus  begins  to  breathe  when  in 
consequence  of  the  expulsory  act  of  parturition  or  detachment 
from  the  placenta,  the  venosity  of  the  foetal  blood  increases  so 
rapidly  as  to  dispel  the  torpor  of  the  respiratory  centres.  In 
many  cases,  however,  when  by  long  travail  the  excitability  of  the 
respiratory  centres  has  become  abnormally  weakened,  the  high 
venosity  of  the  blood  is  not  sufficient  in  itself  to  provoke  the  first 
acts  of  respiration  (asphyxial  foetus).  In  such  cases  it  is  necessary 
to  start  respiratory  activity  by  employing  accessory  stimuli, 
mechanical,  thermal,  or  electrical  (cold  air,  cold  bath,  slaps,  elec- 
trical shocks). 

Under  conditions  of  normal  excitability  of  the  foetal  respiratory 
centres,  the  rapid  increase  of  venosity  in  the  blood  suffices  to  cut 
short  the  iutra-uterine  apnoea  at  the  moment  of  birth,  as  is 
demonstrated  by  numerous  authentic  observations  upon  foetuses 
that  are  still  wrapt  in  their  integuments,  and  sufficiently  protected 
from  the  cold  of  the  air,  and  which  yet  begin  to  breathe  at  the 
simple  interruption  of  the  placeutal  circulation,  or  ligature  of  the 
umbilical  cord.  It  is  easy  to  repeat  this  demonstration  on  the 
foetuses  of  rabbits  or  guinea-pigs  (Engstrorn).  In  the  foetuses  of 
dogs  taken  from  the  uterus  with  the  integuments  intact,  respiration, 
on  the  contrary,  does  not  begin  regularly  until  the  integuments 
are  lacerated  (Pfluger).  In  this  case,  then,  besides  the  interruption 


xin  EESPIRATOEY  RHYTHM  479 

of  the  placental  circulation,  the  action  of  the  external  air  is 
required  to  start  pulmonary  respiration. 

No  one  can  miss  the  analogy  between  foetal  apnoea  and  that 
which  can  be  provoked  on  adult  animals  by  artificial  respiration 
with  the  bellows.  Both  the  one  and  the  other  are  due  to  a  certain 
relation  between  the  venosity  of  the  blood  and  the  excitability  of 
the  respiratory  centres  ;  neither  the  one  nor  the  other  depends  upon 
an  absolute  reduction  in  the  venosity  of  the  blood,  but  rather  upon 
the  low  excitability  of  the  respiratory  centres. 

Under  all  circumstances  in  which  there  is  an  abnormal 
diminution  in  the  excitability  of  the  respiratory  centres,  or  where 
such  conditions  are  produced  experimentally,  it  is  easy  to  obtain  a 
longer  or  shorter  period  of  apnoea,  by  circulating  through  the 
respiratory  centres  a  blood  that  under  ordinary  conditions  is 
adequate  for  the  maintenance  of  respiratory  rhythm. 

In  the  rabbit,  ligature  of  the  two  vertebral  arteries  and  of  one 
carotid  produces  no  conspicuous  change  in  the  respiratory 
mechanism.  But  if  the  second  carotid  is  compressed,  with  arrest 
of  the  cerebral  circulation,  there  will  at  once  be  a  marked  dyspnoea, 
followed  by  epileptiform  convulsions,and  then  by  a  pronounced  delay 
in  the  respiratory  rhythm,  owing  to  the  exhaustion  of  the  centres 
(Kussniaul  and  Tenner).  If  free  course  be  then  given  to  the  flow 
of  blood  through  the  carotid,  there  will  instantly  be  a  period  of 
apnoea,  due  to  the  fact  that  the  stimulation  of  the  centres  by  the 
venosity  of  the  blood  diminishes  rapidly,  while  their  excitability 
is  slowly  re-established  (Gad). 

A  similar  explanation  holds  good  for  the  apnoea  produced 
immediately  after  transfusion  of  blood  (or  even  of  a  simple 
isotonic  solution  of  sodium  chloride)  in  an  animal  which  had 
previously  been  bled  copiously,  so  as  to  produce  asphyxial  dyspnoea, 
and  successive  debilitation  and  retardation  of  respiratory  move- 
ments, owing  to  exhaustion  of  bulbar  excitability  (Gad). 

Similar  to  this  is  the  apnoea  from  vigorous  stimulation  of  one 
peripheral  trunk  of  the  vagus,  which  determines  a  prolonged 
suspension  of  the  beats  of  the  heart.  During  this  inhibition  of 
the  cardiac  systole  arterial  pressure  falls  enormously  (as  we  have 
seen),  in  consequence  of  which  there  is  a  marked  diminution  in 
the  arterial  afflux  to  the  vessels  that  irrigate  the  bulbar  respiratory 
centres.  This  determines  so  pronounced  a  dyspnoea  as,  on  the  one 
hand,  to  subtract  all  the  CO2  from  the  blood  in  the  pulmonary 
vessels,  and  on  the  other,  to  produce  a  certain  degree  of  fatigue  in 
the  said  centres.  When  the  cardiac  beats  are  re-established  and 
the  pulmonary  blood,  strongly  arterialised,  flows  on  to  irrigate  the 
brain,  a  characteristic  suspension  of  the  respiratory  rhythm  ensues, 
because  the  blood  is  apnoeic  in  relation  to  the  somewhat  depressed 
excitability  of  the  centres  (Meyer).  Neither,  then,  is  this  any  "  true 
apnoea"  in  Miescher's  sense  (due,  i.e.,  to  the  positively  apnoeic 


480  PHYSIOLOGY  CHAP. 

character  of  the  blood),  even  if  we  allow  that  the  diminished 
excitability  of  the  bulbar  centres  is  not  the  main  determinant  of 
the  phenomenon. 

XIII.  Voluntary  apnoea,  i.e.  the  temporary  suspension  of 
respiratory  rhythm  that  we  can  produce  upon  ourselves  by  a 
voluntary  effort,  is  a  phenomenon  entirely  different  from  the  cases 
of  apnoea  which  we  have  been  examining.  It  depends  upon  a 
voluntary  inhibition  of  the  rhythmical  activity  of  the  bulbar 
respiratory  centres,  transmitted  by  the  descending  patns  from  the 
so-called  motor  zones  of  the  cerebral  cortex.  When  the  voluntary 
suspension  of  respiration  is  preceded  by  a  certain  number  of 
profound  or  dyspnoeic  respirations  it  may  last  for  a  very  considerable 
time.  Neither  in  the  one  case  nor  the  other,  however,  is  the 
duration  of  this  voluntary  apnoea  in  ratio  with  the  vital  capacity 
of  the  lungs,  nor  with  the  anaemic  or  plethoric  habit,  nor  with 
the  body- weight  and  mass  of  the  tissues  in  the  individual 
experimented  on  (Mosso).  We  may  therefore  conclude  that  the 
resistance  to  asphyxia  is  a  phenomenon  essentially  connected  with 
the  individual  degree  of  excitability  of  the  nerve  centres,  and  is  to 
a  certain  point  independent  of  the  composition  of  the  blood,  or  the 
sum  of  the  stimuli  acting  ab  extrinseco  on  these  centres. 

In  order  to  form  a  clear  notion  of  the  main  objective  differences 
between  voluntary  apnoea  and  the  apnoea  of  artificial  respiration, 
we  need  only  compare  the  tracings  which  show  how  respiratory 
rhythm  is  picked  up  in  the  one  case  and  in  the  other  at  the  close 
of  the  apnoeic  period. 

The  tracings  of  Fig.  215  are  reproduced  from  a  series  of 
researches  which  we  made  at  Bologna  in  1874 :  they  represent 
the  mode  in  which  experimental  apnoea  in  dogs  and  rabbits 
ceases  before  and  after  section  of  the  vagi.  They  show  that 
with  intact  vagi  the  respirations  do  not  immediately  resume 
their  normal  type  when  the  period  of  apnoea  is  over,  but  return 
by  a  slow  increase  in  both  inspiratory  and  expiratory  excursions. 
After  section  of  the  vagi,  when  the  pulmonary  ventilation  has 
been  sufficiently  prolonged,  it  is  not  possible  to  produce  an  apnoea 
lasting  more  than  a  few  seconds ;  but  the  resumption  of  respiratory 
rhythm  only  differs  from  the  preceding  by  a  more  rapid  increase, 
so  that  the  animal  more  promptly  resumes  its  ordinary  rhythm. 

We  do  not  yet  know  how  far  the  increment  consequent  on 
experimental  apnoea  depends  upon  the  growing  venosity  of  the 
blood,  and  progressive  restoration  of  excitability  in  the  bulbar 
centres.  But  it  is  easy  to  show  that  now  one  and  now  the  other 
condition  predominates. 

It  is  a  fact  that  the  venosity  of  the  blood  is  diminished  during 
apnoea,  not  so  much  in  consequence  of  increased  oxygen,  as  because 
the  carbonic  acid  which  it  contains  is  diminished  (P.  Bering). 
On  comparing  the  quantity  of  gases  extracted  from  the  same 


XIII 


KESPIKATOKY  EHYTHM 


481 


animal  before  and  during  experimental  apnoea,  Ewald  found  that 

the  02  content  of  the  arterial  blood  was  hardly  increased  (  +  0*1, 

+  0'9  per  cent)  while  that  of  the  venous  blood  was  considerably 

reduced;  hence  after  apnoea  the  blood,  as  a  whole,  is  poorer  in 


FIG.  215.  —Increase  of  respirations  after  cessation  of  the  apnoea  produced  with  artificial  respiration, 
before  and  after  section  of  vagi,  in  rabbit  and  dog.  (Luciani.)  A,  A',  Adult  rabbit,  tracheo- 
tomised  and  given  artificial  respiration  with  the  bellows ;  A,  respiratory  tracing  consequent 
on  apnoea,  the  trachea  being  connected  with  a  receiver  of  12  litres  air,  which  in  its  turn  com- 
municates with  a  Marey's  writing  tambour ;  A',  the  same,  after  section  of  both  vagi. 
B  and  B',  Puppies  of  3-800  kgrms.  anaesthetised  with  2  c.c.  laudanum  injected  into  a  vein, 
tracheotomy  and  artificial  respiration  with  bellows ;  B,  respiratory  tracing  after  apnoea,  the 
trachea  being  joined  to  a  receiver  of  30  litres  air,  communicating  with  a  writing  tambour  ; 
B',  the  same,  after  cutting  second  left  vagus. 


oxygen.  On  the  other  hand,  the  C02  of  the  arterial  blood 
diminished  by  more  than  half,  while  that  of  the  venous  blood 
increased.  This  fact  is  readily  explained  on  the  assumption 
that  forced  pulmonary  respiration,  by  compressing  the  alveolar 
VOL.  i  2  i 


482  PHYSIOLOGY  CHAP. 

capillaries,  moderates  the  circulation  in  the  lungs,  thus  lessening 
the  work  of  the  heart,  and  lowering  the  pressure  of  the  aortic 
system.  The  blood  in  the  systemic  circulation,  during  ventilation 
with  the  bellows,  remains  longer  in  contact  with  the  tissues,  so 
that  it  loses  more  oxygen  and  gains  more  carbonic  acid ;  in  the 
lesser  circulation,  on  the  contrary,  it  remains  longer  in  contact 
with  the  pulmonary  air,  so  that  it  gains  a  little  more  oxygen  and 
loses  much  more  carbonic  acid.  When  the  forced  respiration 
ceases  a  blood  much  less  venous  than  usual  flows  to  the  brain, 
which  partly  determines  the  apnoea  and  gradual  establishment  of 
respiratory  rhythm,  in  proportion  as  the  blood  circulating  in  the 
bulb  regains  its  normal  degree  of  venosity. 

On  the  other  hand,  it  is  clear  that  the  mechanical  stimulation 
of  the  pulmonary  ending  of  the  vagi  by  forced  ventilation,  which 
is  capable  of  depressing  the  rhythmic  excitability  of  the  bulbar 
respiratory  centres  to  a  very  marked  extent,  must  also  contribute  to 
the  production  of  apnoea  and  the  succeeding  increase  in  respiratory 
rhythm.  In  fact,  under  the  influence  of  the  vagi,  the  apnoea  is  cut 
short  and  practically  disappears,  while  the  successive -increment  in 
rhythm  occurs  more  rapidly.  These  effects  gauge  the  influence 
exerted  on  the  rhythmical  functions  of  the  centres  by  the 
diminished  venosity  of  the  blood,  when  their  excitability  is  not 
altered  in  any  way  by  the  mechanical  action  of  forced  ventilation. 

If  we  contrast  these  analyses  of  experimental  with  that  of 
voluntary  apnoea  it  is  at  once  evident  that  the  two  phenomena  are 
the  effects  of  entirely  different  processes.  Fig.  216  shows  that 
voluntary  apnoea,  when  not  preceded  by  a  voluntary  dyspnoea,  is 
followed,  not  by  increase,  but  by  diminution  in  the  inspiratory 
and  expiratory  excursions,  i.e.  by  a  brief  compensatory  dyspnoea, 
which  ceases  when  the  venosity  of  the  blood  (which  has  increased 
progressively  during  the  suspension  of  respiration)  returns  little 
by  little  to  the  normal  state  on  the  resumption  of  rhythmical 
activity. 

When,  on  the  contrary,  the  voluntary  suspension  of  breathing 
is  preceded  (as  in  Fig.  217)  by  four  forced  inspirations,  the  period 
of  apnoea  is  longer,  and  is  also  followed  by  a  diminution,  though  less 
pronounced  than  the  preceding.  This  confirms  the  statement  that 
exaggerated  ventilation  diminishes  the  venosity  of  the  blood,  and 
depresses  the  excitability  of  the  centres,  through  the  vagi.  If  under 
these  circumstances  the  apnoea  is  not  succeeded  by  an  increment 
this  is  because  the  resumption  of  respiration  is  retarded  by  the 
action  of  the  will,  which  inhibits  the  rhythmical  activity  of  the 
bulbar  respiratory  centres,  via  the  descending  paths  from  the 
brain. 

Neander  (1902)  carried  out  upon  himself  a  number  of  researches 
on  the  respiratory  pause  consequent  on  deep  voluntary  inspirations. 
He  differed  from  Mosso  in  not  prolonging  the  apnoeic  period  to  the 


xiii  EESPIEATOKY  EHYTHM  483 

utmost  by  means  of  voluntary  inhibition.  On  the  contrary,  he 
tried  as  far  as  possible  to  eliminate  this  factor,  turning  his 
attention  away  from  the  respiratory  acts,  so  that  they  should  be  as 
independent  as  possible  of  mental  influences. 

The  results  of  his  researches  differ  from  those  above  described, 
inasmuch  as  the  apnoeic  period  is  followed  not  by  a  measure  of 
compensatory  dyspnoea,  but  by  the  opposite  phenomenon,  i.e.  an 
increment  in  the  inspirations  similar  to  that  exhibited  by  an  animal 
after  the  apnoea  from  artificial  respiration  with  the  bellows. 


'  FIG.  216. — Compensatory  dyspnoea,  consequent  on  period  of  voluntary  apnoea  in  man.     (Mosso.) 
Tracing  recorded  with  Marey's  pneumograph. 

From  his  observations,  as  ?i  whole,  Meander  draws  the  con- 
clusion that  the  apnoea  which  he  studied  must  be  looked  upon  as  a 
combination  of  true  and  spurious  apnoea.  He  found,  in  fact,  that 
its  duration  is  in  ratio  with  the  percentage  quantity  of  the  oxygen 
of  the  expired  air.  On  the  other  hand,  it  starts  as  a  spurious 
apnoea  deriving  from  fatigue  of  the  centres,  since  a  deep  inspiration 


FIG.  217. — Voluntary  apnoea  in  man,  preceded  by  four  forced  inspirations,  and  followed  by  a 
scarcely  visible  decrement.     (Mosso.) 

of  pure  hydrogen  equally  determines  a  marked  pause,  although  of 
brief  duration.  The  prolongation  of  the  pause  consequent  on  a 
series  of  deep  inspirations  must  be  considered  as  the  effect  of 
greater  central  fatigue  combined  with  diminished  venosity  of  the 
blood,  which  becomes  normal  again  during  the  increment  of  the 
succeeding  respirations. 

XIV.  Let  us  see  if  it  is  possible  to  obtain  a  true  apnoea  in 
Miescher's  sense  by  substituting  gentle  continuous  ventilation  of 
the  lungs  for  forced  rhythmical  ventilation,  in  order  as  far  as 
possible  to  avoid  the  mechanical  excitation  of  the  pulmonary 


484  PHYSIOLOGY  CHAP. 

vagus  endings.  This  is  easy  in  birds,  whose  lungs,  as  we  know, 
communicate  via  the  bronchi  both  with  the  bony  chambers,  and 
with  the  diaphragmatic,  axillary,  and  abdominal  air-sacs.  These 
last  are  highly  developed ;  on  opening  the  body  they  are  conspicuous, 
and  when  they  are  pierced,  and  the  walls  of  the  abdomen  held1 
apart  by  a  blepharostat,  the  air  from  a  gasometer,  blown  through 
the  trachea  (under  a  gentle,  regular,  and  continuous  pressure), 
escapes  by  the  ventral  opening. 

Bieletzsky  (1881)  was  the  first  to  attempt  this  experiment. 


FIG.  218. — Gradual  transition  from  normal  respiration  to  apnoea,  with  continuous  pulmonary 
ventilation  in  turkey.  (Luciani  and  Bordoni.)  Ventilation  commences  at  V  at  a  pressure  of 
1  mm.  Hg.  Tracing  recorded  with  a  tambour  with  exploring  lever  .applied  to  sternum,  con- 
nected with  a  tambour  with  writing  lever. 

He  stated  that  he  obtained  perfect  apnoea  lasting  for  the  whole 
time  of  the  inflation.  But  he  made  very  few  experiments;  and 
worse,  he  stopped  half-way,  omitting  the  most  important  part  of 
the  research,  i.e.  that  of  seeing  what  effect  was  produced  by 
continuous  inflation  after  the  section  of  the  vagi  at  the  neck. 

We  resumed  these  experiments  with  Bordoni  at  Florence 
(1888).  The  following  are  the  most  striking  of  our  results,  the 
full  value  of  which,  in  regard  to  a  general  theory  of  respiratory 


Fio.  219.— Continuation  of  previous  tracing  during  prolonged  period  of  apnoea.    At  point  C 
ventilation  ceases,  and  there  is  a  gradual  return  to  normal  respiration. 

rhythm,  can  be  appreciated  now  that  we  have  made  a  physio- 
logical analysis  of  the  various  forms  of  apnoea. 

(a)  In  turkeys,  continuous  ventilation  with  intact  vagi 
constantly  produces  the  apnoeic  state.  When  air  is  insufflated 
with  Waldenburg's  gasometric  apparatus,  at  a  pressure  of  4-5  mm. 
Hg,  apnoea  is  instantaneously  produced  ;  at  a  pressure  of  2-3  mm. 
Hg  the  transition  from  normal  respiration  to  apnoea  occurs,  with 
a  distinct  decrease  in  the  respiratory  acts,  which  is  of  brief 
duration;  finally,  at  a  pressure  of  1-1/5  mm.  Hg  the  decrease 
previous  to  apnoea  is  very  gradual  and  prolonged  (Fig.  218).  The 


XIII 


BESPIKATOEY  EHYTHM 


485 


return  to  normal  respiration  at  the  close  of  insufflation  is 
invariably  preceded  by  an  increase  in  the  respiratory  movements 
(Fig.  219). 

(b)  In  pigeons  also  the  apnoea  is  constant.  At  a  pressure  of 
1-2  mm.  Hg  expiratory  arrest  is  instantaneous  (Fig.  220,  A),  at 
other  times  it  is  preceded  by  a  gradual  decrease  (Fig.  220,  B). 
The  return  to  normal  respiration  is  also  preceded  by  an  increase, 
as  in  the  turkey  (Fig.  221). 


Fia.  220. — Apnoea  from  continuous  ventilation  in  pigeons.  (Lueiani  and  Bordoni.)  A,  Instan- 
taneous transition  from  normal  breathing  to  apnoea,  as  soon  as  ventilation  commences  at  V. 
B  shows  transition  from  normal  respiration  to  apnoea,  after  ventilation  had  commenced  at 
point  V. 

(c)  In  fowls,  apnoea  is  fairly  dimcu-lt  to  obtain,  no  matter  at 
what  pressure  the  pulmonary  ventilation  is  effected.  Generally 
speaking,  it  is  invariably  incomplete,  and  respirations  of  an 
extremely  limited  character  can  always  be  detected,  showing 
persistence  of  rhythmical  activity  in  the  centres  (Fig.  222,  A). 


FIG.  2'21.— Gradual  and  delayed  return  of  normal  respiration  after  prolonged  period  of 
apnoea  in  pigeons.    (Lueiani  and  Bordoni.) 

Here  also  the  return  to  the  normal  is  preceded  by  an  increase 
(Fig.  222,  B). 

(d)  The  apnoea  of  birds  from  continuous  ventilation  is,  like  that 
of  mammals  (Berns),  immediately  interrupted  by  the  insufflation 
of  a  minute  quantity  of  carbonic  acid,  as  also  by  the  momentary 
closing  of  the  ventral  aperture,  or  of  the  inflating  tube,  or  by 
excitation  of  the  vagi  in  the  neck  (Fig.  223). 

(e)  When  pulmonary  ventilation  is  effected  with  pure  oxygen 
instead  of  air,  at  a  pressure  of  1  mm.  Hg,  complete  apnoea  is  never 
produced  in  pigeons  (Fig.  224,  A) ;  at  a  pressure  of  2  mm.  Hg 


486 


PHYSIOLOGY 


CHAP. 


apnoea  is  produced  suddenly  or  with  a  short  decrease  ;  but  the 
resumption  of  respiration  is  preceded  almost  invariably  by  general 
movements  of  the  animal,  without  the  gentle  and  regular  increase 
that  always  succeeds  the  apnoea  produced  by  air  (Fig.  224,  B). 
Often  the  return  occurs  with  periodic  respiration,  which  soon  dies 
away,  and  is  replaced  by  the  ordinary  rhythm  (Fig.  224,  C). 

(/)  After  section  of  the  vagi,  complete  and  persistent  apnoea 
can  no  longer  be  obtained  in  birds,  either  by  inflation  with  air,  or 


FIG.  222. — Effects  of  continuous  pulmonary  ventilation  in  fowls.  (Luciani  tincl  Bordcni.)  A, 
Incomplete  apnoea  after  ventilation  commencing  at  V;  B,  gradual  return  to  normal  respira- 
tion, after  insufflation  ceases,  at  <"• 

with  oxygen,  no  matter  at  what  pressure  the  ventilation  is 
effected.  Eespiration  becomes  weakened  to  a  very  marked  extent 
in  pigeons,  and  to  a  less  degree  in  turkeys  and  fowls  (Fig.  225,  A, 
B,  C).  If  the  vagi  are  divided  during  apnoea,  it  will  usually  persist 
for  a  certain  time,  owing  perhaps  to  the  effect  of  operative 
traumatism.  Sometimes,  however,  the  respiratory  movements  are 
reinstated  immediately  after  section  of  one  vagus  (Fig.  226). 


FIG.  223. — Effect  of  passing  a  small  amount  of  CO*  through  the  respiratory  passages,  during 
apnoea  from  continuous  ventilation,  in  turkeys.    (Luciani  and  Bordoni.) 

Most  of  the  interpretations  of  respiratory  rhythm  suggested 
from  Kosenthal  onwards  (Pfliiger,  Hering,  Kosenbach,  Burkart, 
Marckwald/Gad,  etc.)  start  with  the  fundamental  concept  that 
not  only  nutrition,  but  also  functional  activity,  is  maintained 
in  the  respiratory  centres  by  the  blood  circulating  in  them, 
which,  when  normally  constituted,  acts  as  an  external  stimulus, 
i.e.  it  contains  stimulating  factors  such  as  carbonic  acid  or  the 
other  products  of  tissue  consumption.  This  general  theory  is 
always  based  on  the  apnoea  which  inevitably  sets  in  when 


xiii  KESPIKATORY  RHYTHM  487 

these  stimulating  matters  have  to  any  considerable  extent  been 


pa  .2 
35 


So 
i 

' 


f 


p^a  K 

II 


S5 


removed  from  the  blood,  so  that  it  no  longer  acts  as  an  effective 
stimulus. 


488 


PHYSIOLOGY 


CHAP. 


The  analysis  of  the  different  cases  of  respiratory  rhythm  which 
we  have  so  far  been  examining  rather  lead  us,  on  the  other  hand, 
to  the  conclusion  that  no  apnoea  is  exclusively  determined  by  the 
diminished  venosity  of  the  blood.  Even  the  apnoea  of  birds 
produced  by  continuous  ventilation,  which  Miescher  considered 
the  most  typical  case  of  true  apnoea,  is,  according  to  our  results, 
a  complex  effect,  essentially  determined  by  a  vagus  reflex. 
Indeed,  when  the  pressure  by  which  pulmonary  ventilation  is 
effected  is  strong  enough,  it  is  instantaneously  produced,  without 
any  gradual  diminution  of  the  respiratory  acts,  i.e.  before  any 
decarbonisation  of  blood  can  have  taken  place.  Accordingly, 
it  must  depend  essentially  on  reflex  excitation  by  the  centripetal 


Fio.  225. — Effect  of  continuous  ventilation  after  section  of  vagi  in  birds.  (Luciani  and  Bordoni.) 
A,  In  pigeon  ;  B,  in  turkey  ;  C,  in  fowl.  In  all  three  tracings  the  insufflation  of  air  commences 
at  V. 

paths  from  the  lungs  and  air-sacs,  in  which  the  air  is  normally 
but  little  regenerated,  and  which,  accordingly,  are  highly  sensitive 
to  the  passage  of  air,  even  at  low  pressures. 

In  fowls  apnoea  is  hard  to  obtain,  perhaps  because  their  air- 
sacs  are  less  sensitive  to  the  mechanical  action  of  air.  Striking 
evidence  of  this  theory  is  afforded  by  the  fact  that  after  section  of 
the  vagi  it  was  no  longer  possible  to  obtain  complete  apnoea  in  any 
of  the  birds  experimented  on.  The  decarbonisation  of  the  blood 
reduces  the  respiratory  processes  considerably,  but  it  does  not 
suppress  them,  which  upsets  the  usually  accepted  theory  that 
respiratory  rhythm  is  maintained  by  the  external  stimuli  of  the 
blood  or  interstitial  lymph,  circulating  in  the  centres. 

No  less  interesting  (although  of  doubtful  significance)  is  the 


-r.  o 


xin  KESPIEATOEY  EHYTHM  489 

fact  that  with  intact  vagi  it  is  not  possible  to  obtain  complete 

apnoea,  when  continuous  ventilation  is  made 

with  pure  oxygen  instead  of  air.     Is  it  possible 

that  oxygen  lowers  the  tone  or  paralyses  the 

afferent  fibres  of  the  vagi,  so  that  the  respiratory 

centres  resume  partial  or  total  independence  of 

their  rhythmical  and  alternate  messages  ?     Or 

does   oxygen    perhaps   excite    the    peripheral 

extremities  of  these  nerves  to  such  an  extent 

as  to  throw  into  reflex  activity  other  centres, 

which  in  functioning  counteract  the  inhibitory 

messages  to  the  centres  of  respiration  ?     The 

general   movements   and    restlessness   of    the 

animal  on  ventilation  with  oxygen,  rather  tends 

to   support    this   second   hypothesis.      At   all 

events   this   curious   phenomenon    is   a    fresh 

argument  towards  showing  that  the  decarbon- 

isation  of  blood  and  its  marked  arterialisation 

is  not  enough    to  check  the  rhythmical  and 
alternate  activity  of  the  respiratory  centres. 

Ehythmical  and  alternate  activity!  That 
is  to  say,  rhythmical  activity  of  the  inspira- 
tory  centres,  alternating  with  rhythmical 
activity  of  the  expiratory  centres,  even  in 
apnoea,  even  during  the  quiet  expiration  of 
sleep  !  This  fact — which,  as  we  have  seen,  was  ^^^^^ 

clearly  demonstrated  by  Aducco — excludes  the  ^^|^^H  1 1 
assumption  that  the  mechanical  activity  of 
respiration  depends  upon  any  kind  of  external 
stimulus.  So  that  it  does  not  appear  to  us 
possible,  in  explaining  the  alternate  activity  of 
two  centres  that  are  antagonistic  in  action,  to 
invoke  as  a  causal  factor  an  external  stimulus 
of  any  kind  whatsoever,  acting  continuously 
upon  these  centres. 

We  can  only  conclude  that  the  activity  of    ^^^^^^^ 
the  said  respiratory  centres  depends  essentially     IBH 
upon  the  special  intrinsic  organisation  of  the 
elements  of  which  they  are  composed.  ^^^^^^^ 

These  elements  are  not  merely  endowed 
with  reflex  excitability,  i.e.  are  thrown  into 
excitation  by  simple  external  stimuli,  coming 
to  them  in  the  form  of  nervous  vibrations 
from  the  periphery  of  the  centripetal  nerves, 
or  as  the  chemical  products  of  tissue  con- 
sumption acting  directly  upon  those  tissues  ;  but  they  also  possess 
automatic  excitability  properly  so-called,  i.e.  they  are  capable  of 


03     r- 


490  PHYSIOLOGY  CHAP. 

reacting  to  internal  stimuli,  by  intrinsic  variations  in  their 
metabolism. 

This  logical  deduction  from  a  long  series  of  premisses  appears 
at  first  sight  to  be  contradicted  by  some  of  Fredericq's  latest 
experiments  (1901).  He  claims  to  have  obtained  true  apnoea  upon 
dogs,  by  eliminating  (with  the  simple  reduction  of  the  carbonic 
acid  of  the  blood  circulating  in  the  centres)  certain  mechanical 
causes  that  act  through  the  afferent  paths  of  the  pulmonary  vagi. 

The  experimental  method  which  he  employed  for  this  purpose 
is  extremely  ingenious,  although  not  easy  to  carry  out.  It  consists 
in  establishing  between  two  dogs  the  so-called  crossed  cephalic 
circulation.  It  is  necessary  to  connect  the  carotids  of  the  animals 
by  glass  cannulae  and  rubber  tubes  (after  ligaturing  the  vertebral 
arteries,  and  rendering  the  blood  incoagulable  by  injections  of 
pro-peptone)  so  that  the  central  end  of  the  carotid  in  one  and  the 
peripheral  end  of  the  carotid  in  the  other  are  brought  together, 
•and  vice  versa.  The  blood  being  circulated  in  this  new  system,  it 
follows  that  the  brain  -of  the  first  animal  is  irrigated  by  the 
greater  part  of  the  blood  derived  from  the  heart  Of  the  other 
animal,  and  vice  versa. 

Under  these  conditions,  Fredericq  observed  that  the  artificial 
increase  and  reduction  of  venosity  in  the  blood  of  one  of  the  dogs 
affected  the  respiratory  centres  of  the  other,  which  exhibited 
dyspnoea  or  apnoea  respectively.  If,  e.g.,  the  trachea  was  compressed 
in  dog  A  so  as  to  produce  asphyxia  in  that  animal,  the  blood 
surcharged  with  waste  products,  on  reaching  the  brain  of  dog  B, 
determined  a  violent  dyspnoea,  while  dog  A  continued  to  breathe 
quietly,  or  showed  a  slight  inclination  to  apnoea,  its  centre  being 
irrigated  with  blood  from  B  which  was  highly  arterial,  in  conse- 
quence of  the  dyspnoeic  respiration  of  the  latter. 

If,  on  the  contrary,  profound  artificial  respiration  with  the 
bellows  is  performed  on  dog  B,  perfect  apnoea  is  seen  on  dog  A, 
which,  according  to  Fredericq,  can  only  depend  upon  the  reduced 
venosity  of  the  blood  circulating  in  its  respiratory  centres  from 
the^heart  of  B,  all  abnormal  mechanical  action  of  the  lungs  being 
thus  eliminated  in  A  (Fig.  227). 

On  determining  with  the  aerotonometer  the  state  of  the  gases 
in  the  blood  of  dog  A  during  artificial  respiration,  Fredericq  found 
a  slight  rise  in  the  percentage  content  of  oxygen,  and  conversely 
a  marked  reduction  (by  more  than  half)  in  the  percentage  of 
carbonic  dioxide.  From  this  he  concluded  that  the  apnoea  that 
obtains  during  crossed  cephalic  circulation  is  exclusively  deter- 
mined by  diminished  tension  in  the  carbonic  acid  of  the  blood. 
Have  we  here,  for  the  first  time,  evidence  of  a  true  apnoea,  in 
Miescher's  sense,  determined  by  the  state  which  Mosso  calls  acapnia? 

On  carefully  considering  the  experimental  conditions  of 
Fredericq's  method  it  becomes  apparent  that  he  is  far  from 


xin  RESPIRATORY  RHYTHM  491 

having  demonstrated  that  the  respiratory  acts  are  normally  deter- 
mined by  the  carbonic  acid  circulating  in  the  centres.  Baglioni 
and  Winterstein  aptly  pointed  out  that  in  Fredericq's  experiment 
the  vagi  were  left  intact.  Now,  when  the  excitability  of  the 
respiratory  centres  is  altered,  it  is  quite  conceivable  that  the 
excitations  of  the  pulmonary  terminations  of  the  vagi,  which 
normally  exert  a  reflex  control  over  the  acts  of  respiration,  may 
determine  an  inhibition  of  the  centres,  and  thus  produce  spurious 
apnoea.  That  in  Fredericq's  cases  the  excitability  of  the  centres 
was  enormously  depressed  may  be  inferrecNhrom  the  narcosis  (due 
to  the  morphin  or  chloroform  administered),  the  operations 
necessary  to  produce  the  crossed  circulation  in  the  brain,  the 
diminished  blood-supply  to  the  brain  (ligature  of  vertebral 


FIG.  227. — Pneumograms  obtained  from  two  Knoll's  pnetimographs  in  two  dogs  (A  and  B)  during 
experimental  crossed  circulation.  (Fredericq.)  The  blood  from  trunk  of  B  circulates  in  head  of 
A;  that  from  trunk  A  in  head  B.  Each  application  of  artificial  respiration  in  B  produces  a 
short  period  of  apnoea  in  A. 

arteries),  and  lastly,  the  general  intoxication  of  the  centres  due 
to  the  injection  of  pro-peptone,  which  induces  a  quasi-comatose 
state.  It  is  also  conceivable  that  under  such  conditions  the  sum 
of  the  excitations  which  reach  the  bulbar  centres  continuously 
by  the  afferent  paths  of  the  pulmonary  vagi,  the  muscles,  fascia, 
tendons,  determine  a  brief  inhibition  of  the  respiratory  movements. 
We  say  brief,  because  Fredericq  has  not  demonstrated  that  pro- 
longed artificial  respiration  in  dog  B  determines  any  apnoeic  state 
of  corresponding  duration  in  dog  A. 

The  tracings  of  Fig.  22*7,  on  the  other  hand,  demonstrate  that 
in  two  repeated  experiments  five  strong  pulmonary  insufflations 
on  dog  B  determine  a  suspension  of  respiration  in  dog  A  lasting 
8-10  seconds,  after  which  natural  respiration  re-commences  very 
feebly,  in  accordance  with  the  depressed  excitability  of  the  centres. 


492 


PHYSIOLOGY 


CHAP. 


XV.  Just  as  the  phenomenon  of  periodic  cardiac  rhythm 
supplied  the  most  direct  argument  in  favour  of  the  theory  of  the 
automatic  functions  of  the  heart,  so  that  of 
periodic  respiration,  or,  at  least,  of  certain 
forms  which  it  may  assume,  gives  us  direct 
evidence  of  the  automaticity  of  the  respir- 
atory centres. 

Periodic  respiration,  in  its  most  classic 
form,   as    first    described    by    the    English 
physicians  Cheyne  and  Stokes  (1816-1854), 
consists  in  an   alternation  of   apnoea    and 
dyspnoea,  of  pauses  and  groups.     Each  group 
A     of  respirations  shows  a  rise  and  successive 
|     fall  of  intensity  as  well  as  frequency.     The 
|    first  and  last  respirations  are  minimal  or  at 
5     any  rate   quite  shallow,  while  the   central 
§     respirations   are  deep   or  highly  dyspnoeic. 
Each  group  may  reach  a  maximum  of  20-30 
respirations.      The  duration  of  'the   pauses 
§     may  be  equal  to,  less  than,  or  greater  than 
B     that  of  the  groups;  but  it  is  always  above 
|    40-50." 

\  These  classical  cases  of  periodic  group- 

-.  ing  of  the  respiratory  acts  are  rare,  and  are 
|  usually  met  with  in  serious  disease  of  the 
|  brain  and  heart,  in  the  comatose  period  of 
I*  certain  acute  infections,  and  in  the  later 
£  pre-agonic  stage  of  various  diseases.  A 
2  typical  case  of  Cheyne-Stokes  breathing  is 
g  that  observed  by  Gibson  (Fig.  228)  in  a  man 

1  suffering  from  chronic  renal  disease  of  the 
f'    kidneys.     Less  intense  forms,  on  the   con- 
8     trary,  in  which  the  groups  are  represented 

2  by  a  few  respirations  and  the  pauses  give 
intermittency  for  a  few  seconds  (Fig.  229  A) 
are  tolerably  frequent.    The  pauses  may  even 
be  absent,  when  the  periodicity  of  breathing 
is  reduced  to  the  rise  and  fall  in  intensity 
of  the  respiratory  acts,  which  succeed  with 
a  certain  rhythm,  with  no  positive  distinc- 
tion of  groups  and  pauses  (Fig.  229,  B). 

The  most  important  thing  to  note  in  all 
these  forms  of  periodic  respiration  is  that 
the  duration  of  the  pauses  is  not  in  any 
relation  with  the  duration  or  number  of  the 
respirations  in  the  groups.  Of  great  significance,  again,  is  the  fact 
that  the  form  of  the  groups  may  vary  considerably ;  sometimes 


XIII 


KESPIKATOKY  EHYTHM 


493 


they  exhibit  an  increment  and  decrement  (Fig.  230) ;  at  other 
times  an  increment  alone  (Fig.  230) ;  at  others  a  decrement  alone 
(Fig.  231) ;  at  others  again  the  respirations  of  the  group  all  exhibit 
much  the  same  intensity. 


FIG.  229. — Periodic  respiration  observed  in  man  at  high  altitudes.  (Mosso.)  A,  Tracing  obtained 
with  Marey's  pneumograph  on  Mosso  himself  when  awake,  at  3620  metres.  B,  Tracing  taken 
during  light  sleep  from  watchman  at  the  Regina  Margherita  hut,  4500  m. 

Periodic  respiration  is  not  essentially  a  morbid  phenomenon. 
It  invariably  accompanies  the  lethargy  of  hibernating  animals 
(Mosso,  Fano,  Langendorff,  Patrizi) ;  is  sometimes  seen  in  the  sleep 


FIG.  230. — Periodic  respiration  in  man.    (A.  D.  Waller.)    The  rotating  cylinder  moves  slowly. 
The  signal  marks  minutes  on  abscissa. 

of  healthy  individuals,  particularly  in  old  people  and  children 
(Mosso) ;  often  at  high  altitudes  (2500-4500  m.  above  sea-level) ; 
it  is  observed  conspicuously  in  sleep  (Fig.  231),  and  in  a  less  degree 
in  waking  (Egli-Sinclair,  Mosso). 

A  number  of  attempts  have  been  made  to  evoke  experimental 


494 


PHYSIOLOGY 


CHAP 


periodic  respiration  in  man  or  other  animals.  Flourens  (1842) 
accidentally  observed  periodic  respiration  in  an  animal  on  which, 
after  extirpating  the  brain,  the  two  vagi  had  been  divided.  M. 
Schiff  (1859)  described  the  same  phenomenon  in  mammals  after 
copious  haemorrhage  and  pressure  exerted  upon  the  medulla 
oblongata. 

Traube  (1871)  induced  periodic  respiration  in  cases  of  heart 


Fia.  231.— Periodic  respiration  observed  on  U.  Mosso  during  sleep,  4o60  metres. 

disease  by  hypodermic  injection  of  morphia,  and  increased  it  by 
the  same  means  in  patients  who  already  exhibited  the  phenomenon. 

In  1874  we  obtained  the  same  effect  in  dogs,  by  giving  them 
intravenous  injections  of  laudanum  and  subsequent  artificial 
respiration  sufficient  to  produce  apnoea  (Fig.  232). 

Filehne  and  Heidenhain  (1874)  simultaneously  obtained  it  in 
dogs  and  rabbits  with  intravenous  injections  of  chloral  hydrate. 


Fio.  232.— Periodic  respiration  in  dog  anaesthetised  by  intravenous  injection  of  u  c.c.  laudanum. 
Tracheotomy  was  performed  after  previous  production  of  apnoea  by  artificial  respiration  with 
the  bellows.  (Luciani.)  The  tracing  was  obtained  by  connecting  the  tracheal  tube  with  a 
receiver  containing  30  litres  of  air,  joined  to  a  writing  tambour. 

Cuffer  (1878),  who  had  noticed  the  frequent  coincidence  of  the 
respiratory  phenomenon  with  interstitial  nephritis,  succeeded  in 
provoking  it  in  dogs  by  intravenous  injections  of  creatine  and 
ammonium  carbonate.  Smirow  (1884)  obtained  it  in  dogs  with 
inhalations  of  sulphuretted  hydrogen ;  Langendorff  (1881)  with 
injections  of  muscarine  and  digitaline;  Bordoni  (1886)  with 
injections  of  scillaine  and  gelsemine,  on  frogs  and  toads. 

After  discovering  the  cardiac  phenomenon  in  the  frog  (1872- 
1873,  in  Lud wig's  laboratory)  we  attacked  the  experimental  study 


xin  RESPIRATORY  EHYTHM  495 

of  the  respiratory  phenomenon,  with  the  object  of  verifying  whether 
the  two  effects  (which  present  such  a  marked  analogy)  had  a 
common  origin.  Since  the  cardiac  effect  is  instantly  and  con- 
spicuously obtained  upon  the  isolated  heart  perfused  with  serum, 
when  the  most  automatic  part  of  the  frog's  heart  is  cut  off  by  a 
ligature,  we  inquired  whether  the  respiratory  effect  would  be 
produced,  on  transversely  dividing  the  spinal  bulb  in  the  rabbit, 
above  the  origin  of  the  vagus  nerves,  so  as  to  separate  its  highest 
segment  from  the  respiratory  centres.  These  investigations 
(c'arried  out  like  the  former  in  Ludwig's  laboratory)  were  long 
and  laborious,  because  not  always  successful.  Sometimes  we 
obtained  respiratory  standstill,  immediately  or  soon  after  the 
section.  At  other  times  there  was  no  radical  modification  of 
respiratory  rhythm,  which  (although  it  became  irregular  and  pro- 
gressively slow  and  shallow  till  death  occurred)  never  presented 
the  peculiar  grouping  characteristic  of  Cheyne-Stokes  breathing. 


FIG.  233. — Periodic  respiration  in  rabbit,  after  transverse  section  of  bulb  at  level  of  visible  apex 
of  alae  cinereae.  (M.  Marckwald.)  Tracing  taken  with  phrenograph.  The  ascending  curves 
correspond  with  the  contractions  of  the  diaphragm. 

But  in  other  more  fortunate  cases  it  did  appear  in  the  form 
of  groups,  which  exhibited  no  increment  but  merely  a  rapid 
decrement  followed  by  the  pause.  The-  number  of  respirations 
in  the  successive  groups  increased  or  diminished  somewhat 
irregularly ;  at  the  same  time  the  pauses  became  now  longer,  now 
shorter  than  the  groups.  In  the  most  successful  experiment, 
however,  we  were  able  to  watch  the  tendency  of  the  groups  to 
become  gradually  smaller,  and  of  the  pauses  to  shorten,  till  the 
crisis  of  the  phenomenon  set  in,  when  the  groups  resolved  them- 
selves into  a  series  of  staccato  respirations  separated  by  long 
pauses,  and  progressively  decreasing  till  death  ensues.  The  vary- 
ing position  of  the  section  on  the  bulb,  and  the  different  degrees 
of  the  consequent  haemorrhage,  appear  to  us  sufficient  to  account 
for  the  difference  in  results. 

Marckwald  (1888)  obtained  precisely  similar  results  in 
Kronecker's  laboratory  on  separating  the  medulla  oblongata  from 
the  rest  of  the  brain  at  a  level  above  the  respiratory  centres  of 


496  PHYSIOLOGY  CHAP. 

the  rabbit.  When  the  section  falls  at  the  level  of  the  apex  of  the 
alae  cinereae,  respiration  immediately  becomes  periodical.  After 
long  pauses  groups  of  three,  four,  or  five  respirations  occur,  which 
decrease  in  depth  (Fig.  233).  On  dividing  the  medulla  at  a 
higher  point,  periodic  respiration  may  sometimes  be  observed  when 
pressure  is  exerted  on  the  respiratory  centres  by  the  extravasation 
of  blood  in  the  neighbourhood  of  the  alae  cinereae.  On  removing 
the  clot  ordinary  respiration  is  reinstated.  Sometimes,  after  section 
of  the  bulb,  respiration  will  at  first  be  normal  and  subsequently 
become  periodic,  perhaps  owing  to  the  exposure  of  the  bulb  to  air. 
In  conclusion — no  essential  difference  from  the  results  we  pub- 
lished eight  years  previously. 

In  1874,  on  studying  the  course  of  asphyxia  in  narcotised  and 
tracheotomised  dogs,  with  intact  or  divided  vagi,  making  them 
breathe  into  a  large  closed  receiver,  which  transmitted  the  respiratory 
movements  to  a  writing  tambour,  we  not  infrequently  observed,  in 
the  final  moments  before  the  death  of  the  animal,  the  formation 
of  a  series  of  small  groups  consisting  of  two  respirations,  the  first 
being  somewhat  deeper  than  the  second,  separated  by  pauses 
occupying  a  period  about  three  times  as  great  as  that  of  the 
groups  (tracings  similar  to  that  of  Fig.  231).  So  that  the  mode 
in  which  the  vitality  of  the  respiratory  centres  dies  out  in 
asphyxia  recalls  the  modus  moriendi  of  the  frog's  heart,  when 
excised  and  filled  with  serum  that  is  never  regenerated  (see 
Chap.  IX.  3). 

In  1880  Sokolow  and  Luchsinger  published  their  ingenious 
researches  on  the  respiratory  phenomenon  observed  in  the  frog, 
during  asphyxia  of  the  centres  from  ligature  of  the  aorta,  and 
during  the  resumption  of  activity  when  the  ligature  has  been 
removed.  They  noticed  that  in  the  first  case  the  number  of 
respirations  in  the  successive  groups  diminishes,  while  the  subse- 
quent pauses  are  prolonged  ;  in  the  second  case  the  opposite  occurs, 
i.e.  the  groups  become  progressively  larger  and  the  pauses  shorter 
until  normal  rhythmical  respiration  is  resumed.  We  have  no 
information  as  to  the  form  of  the  groups,  the  authors  not  having 
employed  the  graphic  method. 

The  important  researches  of  Fano,  carried  out  in  our  laboratory 
at  Florence  in  1883,  on  the  periodic  respiration  of  tortoises, 
agree  perfectly  with  those  of  Sokolow  and  Luchsinger,  although 
they  grew  out  of  a  side  issue.  After  excising  the  heart  of  a  big 
land  tortoise  he  saw  that  the  animal  continued  to  breathe,  no 
longer  rhythmically,  but  in  groups  separated  by  long  pauses. 
Periodic  respiration  (though  of  a  highly  irregular  character  in 
regard  to  number  of  respirations  and  duration  of  groups  and 
pauses)  is  very  frequently  observed,  both  in  land  and  water 
tortoises,  during  the  winter  lethargy.  In  the  majority  of  groups 
the  respirations  present  much  the  same  amplitude,  and  none  of 


xin  EESPIKATOBY  KHYTHM  497 

them  exhibit  the  characteristic  rise  and  fall  of  the  classical  Cheyne- 
Stokes  phenomenon  (Fig.  234). 

On  trephining  the  carapace  of  such  an  animal,  opening  the 
pericardium  and  ligaturing  the  pulmonary  artery  and  the  two 
aortae  with  a  single  thread,  so  as  to  arrest  the  circulation,  the 
respiratory  phenomenon  continues ;  the  pauses  lengthen,  the 
groups  shorten,  so  that  the  periodicity  of  the  rhythm  becomes 
more  marked. 

When  these  hibernating  tortoises  are  made  to  breathe  in- 
different gases  such  as  nitrogen  and  hydrogen,  instead  of  air  or 
pure  oxygen,  the  periodic  respiration  continues  to  be  of  the  same 
character ;  dyspnoea  is  entirely  absent,  while  the  number  of 
respirations  in  the  time  unit  becomes  much  less.  Respiration 
with  indifferent  gases  may  be  kept  up  for  a  long  time,  without 
cessation  of  life  in  the  animal.  Thus,  e.g.,  a  tortoise  continued  to 
breathe  for  two  days  in  an  atmosphere  of  pure  nitrogen. 

None  the  less,  protracted  respiration  of  asphyxial  or  toxic 
gases,  such  as  carbonic  acid  and  carbon  monoxide,  does  suppress 


Fio.  -234.— Periodic  respiration  in  hibernating  tortoise.     (Fano.)     Pneuniograms  obtained  by 
letting  animal  breathe  from  small  receiver,  connected  with  a  writing  tambour. 

periodic  respiration  in  the  hibernating  tortoise.  «vln  certain  cases 
carbonic  acid  produces  an  inclination  to  dyspnoea,  but  only  of 
brief  duration.  In  all  cases,  whether  suddenly  or  after  a  short 
time,  the  pauses  become  longer,  the  groups  of  respirations  less 
frequent  and  smaller,  until  they  die  out.  A  water  tortoise 
breathed  18  litres  of  carbon  monoxide  for  :36  hours.  It  was 
removed  from  the  apparatus  after  its  breathing  had  ceased  for 
about  an  hour ;  yet  it  was  still  alive,  and  after  a  little  time  began 
to  breathe  again  and  to  move  spontaneously.  When  killed  and 
dissected  it  showed  the  most  unmistakable  signs  of  carbon 
monoxide  poisoning. 

When  a  hibernating  tortoise  is  chloroformed,  there  is  a  rapid 
and  progressive  diminution  in  the  groups  of  respirations  till 
absolute  standstill  of  the  respiratory  centres  is  obtained.  Chloro- 
form, the  "reagent  for  vital  excitability,"  as  it  was  termed  by  Cl. 
Bernard,  attacks  the  innermost  conditions  of  the  activity  of  the 
nerve-centres,  removing  from  the  respiratory  centres  in  a  short 
time  their  capacity  to  liberate  the  energy  which  they  accumulate 
by  the  accustomed  paths. 

VOL.  I  2K 


498  PHYSIOLOGY  CHAP. 

XVI.  Periodic  respiration  is  a  physio-pathological  phenomenon 
intimately  connected  with  the  difficult  problem  of  the  nature  of 
the  normal  rhythmical  functions  of  the  respiratory  centres.  Th/$, 
first  to  perceive  the  importance  of  this  point  was  Traube,  to  whose 
initiative  is  due  the  harvest  of  literature  on  this  interesting 
subject,  which  we  have  briefly  summarised. 

In  1879  we  drew  up  an  exhaustive  refutation  of  Traube's 
doctrine,  and  of  the  more  complicated  theory  opposed  to  it  by  Filehne 
in  1874,  showing  the  absolute  inadequacy  of  these  hypotheses  to 
account  for  the  whole  of  the  experimental  data,  and  the  great 
variety  of  clinical  forms,  which  the  respiratory  phenomenon  may 
assume.  We  showed  that  it  was  impossible,  in  face  of  the  proved 
facts,  to  solve  the  problem  by  the  postulate  usually  admitted  and 
defended,  to  the  effect  that  the  capacity  and  functional  activity  of 
the  central  mechanisms  of  respiratory  rhythm  are  always  in 
direct  and  immediate  dependence  upon  extrinsic  conditions  of 
stimulation  and  nutrition ;  i.e.  in  other  words,  that  the  said 
centres  merely  transform  what  at  any  given  moment  they  receive, 
in  the  same  degree  and  with  the  same  rhythm  at  which  they 
receive  it.  The  experimental  evidence  shows  that  there  is, 
between  the  external  action  and  the  reaction,  a  whole,  complex, 
chemico- molecular,  internal  process,  of  which  we  are  aware  in 
virtue  of  its  results,  but  as  to  the  laws  of  which  we  are  entirely 
ignorant. 

The  obvious  facts  on  which  we  have  insisted  amply  suffice  to 
prove  that  there  is  no  ratio  between  the  duration  and  the  degree 
of  pulmonary  ventilation  represented  by  the  groups  and  the 
duration  of  the  pauses ;  that  the  form  of  the  groups  may  vary 
greatly  and  in  opposite  ways  that  are  not  comparable  inter  se  ; 
that  periodic  respiration  may  be  observed  even  where  no  gas 
exchanges  between  the  atmosphere  and  the  blood  are  possible 
— all  these  clearly  demonstrate  the  fundamentally  automatic 
character  of  the  function  of  the  bulbar  respiratory  centres.  "  The 
different  forms  that  may  be  assumed  by  the  respiratory  rhythm, 
including  those  of  periodic  grouping,  are  merely  the  external 
expression  of  corresponding  modes  of  oscillation  in  the  nutritional 
processes,  which  are  carried  on  within  the  depths  of  the  respiratory 
centres  "  (Luciani,  1879). 

Normally,  however,  these  centres,  in  addition  to  an  automatic 
excitability,  are  provided  with  a  most  delicate  reflex  excitability, 
which  enables  them  immediately  to  react  even  to  the  slightest 
external  stimulus,  thus  giving  rise  to  profound  modifications  in 
the  form  and  rhythm  of  the  automatic  excitability  as  dependent 
upon  the  internal  impulses.  Our  task  is  now  to  determine  (as 
precisely  as  possible)  what  are  the  relations  of  co-existence 
of  these  two  forms  of  excitability,  both  in  normal  conditions,  and 
under  exceptional  or  abnormal  conditions,  of  the  respiratory  centres. 


xin  RESPIRATORY  RHYTHM  499 

The  normal  respiratory  rhythm  of  man  and  other  homothermic 
animals  in  general  is  essentially  conditioned  by  the  reflex  activity 
of  the  centres.  In  eupnoea  it  is  the  established  auto-regulation  of 
the  vagi  that  predominates,  i.e.  the  mode  in  which  the  air  that 
passes  rhythmically  through  the  lungs  in  a  certain  time  is 
distributed,  depends  on  the  rhythmical  and  alternate  impulses 
that  reach  the  centres  from  the  peripheral  extremities  of  the 
pulmonary  vagi.  The  proof  of  this  lies  in  the  fact  that  normally 
the  nervous  and  muscular  mechanisms  of  the  thoracic  movements 
are  always  active  ;  inspirations  alternate  with  expirations  without 
pause  or  intermediate  rest  (cf.  tracings  of  Figs.  184,  185,  186,  on 
pp.  418,  420,  421),  as  if  the  excitation  passed  from  the  inspiratory 
to  the  expiratory  centres,  and  vice  versa,  by  an  uninterrupted 
reciprocal,  intercentral  transmission,  and  with  a  delay  that  just 


FJ«.  -23.J.— Thoracic  respiration  of  a  soldier,  recorded  with  Marey's'pneuniograph 

at  4560  metres.     (A.  3Iosso.) 

suilices  for  the  two  antagonistic  movements  to  succeed  without 
coincidence. 

Under  certain  special  conditions,  however,  tins  perfect  eupnoea 
fails,  probably  in  consequence  of  a  diminished  sensibility  of  the 
afferent  fibres  of  the  vagi,  which  renders  the  impulse  transmitted 
to  the  inspiratory  centres  from  the  expiratory  position  of  the 
lungs  nil  or  inadequate.  In  this  case  there  is  between  the  end  of 
expiration  and  the  commencement  of  inspiration  a  more  or  less 
prolonged  pause.  This  phenomenon,  which  we  believe  to  be  not 
uncommon  in  clinical  cases,  was  recorded  graphically  by  Mosso  in 
two  robust  soldiers  during  rest  upon  the  High  Alps  (4560  m.  above 
sea-level),  as  shown  in  the  tracing  of  Fig.  235.  We  do  not 
interpret  this  as  meaning  that  at  high  altitudes  one  breathes  less, 
since  it  is  shown  elsewhere  that  "  at  high  altitudes  no  important 
modifications  in  the  output  of  carbonic  acid  and  the  .intake  of 
inspired  air  occurs."  Until  the  contrary  is  proved,  we  hold  it 
logical  to  assume  that  the  phenomenon  described  depends  upon  a 

VOL.  i  2  K  a 


500  PHYSIOLOGY  CHAP. 

paretic  state  of  the  vagus,  determined  by  the  altitude.  In  this 
case  the  eupnoea  is  no  longer  perfect,  and  the  iuspiratory  acts  are  no 
longer  determined  by  the  nervous  vibrations  that  ascend  by  the 
afferent  paths  of  the  vagus  to  the  centres,  but  by  a  certain  degree 
of  venosity  acquired  by  the  blood  circulating  in  them  during  the 
expiratory  pause. 

While  the  intermittent  excitations  via  the  centripetal  nerve- 
paths  determine  particularly  the  frequency  of  rhythm,  i.e.  the  distri- 
bution of  the  total  air  that  passes  through  the  lungs  in  the  time 
unit,  the  chemical  excitation  produced  by  the  venosity  of  the  blood 
especially  determines  the  intensity  of  the  rhythm,  i.e.  the  total 
quantity  of  air  breathed  in  the  time  unit.  The  theory  of  dyspnoea 
agrees  perfectly  with  this  conclusion.  In  dyspnoea,  in  general,  and 
particularly  in  that  determined  by  the  increased  production  of 
carbonic  acid,  the  reflex  excitability  of  the  centres  comes  into 
play,  and  causes  automatic  excitability  to  become  latent  by 
adapting  the  respiratory  rhythm  to  the  chemical  needs  of  the 
organism. 

As  in  apnoea  and  dyspnoea  the  factor  of  the  central-  excitations 
determined  by  the  amount  of  the  external  stimuli  predominates, 
so  in  tachypnoea  and  apnoea  the  factor  of  increased,  or  diminished, 
excitability  predominates,  owing  to  which  the  centres  become  more 
sensitive,  or  refractory,  to  the  action  of  the  said  stimuli. 

But  the  excitability  of  the  centres  (whether  automatic  or 
reflex)  is  an  oscillating  quantity,  which  follows  closely,  and  is,  so 
to  speak,  modelled  on  all  the  vicissitudes  of  the  intimate  metabolic 
processes.  Each  explosion  of  energy  that  accompanies  a  katabolic 
disruption  determines  a  relative  degree  of  resistance  in  the 
centres  to  external  and  internal  stimuli ;  each  accumulation  of 
energy,  determined  by  an  anabolic  construction,  increases  their 
susceptibility  to  the  same.  Further,  these  respiratory  tracings 
show  not  merely  the  rhythmic  and  alternate  activity  of  the 
antagonistic  respiratory  muscles,  but  they  sometimes,  particularly 
after  the  action  of  certain  poisons,  exhibit  slow  positive  and 
negative  oscillations  in  the  tone  of  the  said  muscles,  which  recall 
the  oscillations  of  tone  in  the  auricles,  as  described  by  Fano,  and 
in  the  vessels,  as  described  by  Schiff  and  by  Traube  and  Hering. 
This  is  well  illustrated  in  the  tracing  of  Fig.  236,  registered 
by  Mosso  from  a  rabbit  intoxicated  with  piridine.  Under  normal 
conditions  these  oscillations  in  the  tone  of  the  respiratory  muscles 
are  absent,  but  occasionally  they  become  visible  in  sleep  as  in 
Fig.  237-  These  slow  oscillations  in  the  tone  of  the  muscles 
are  the  external  expression  of  the  corresponding  oscillations  of 
excitability  (automatic  and  reflex)  in  the  respiratory  centres. 

As  soon  as  these  oscillations  of  excitability  of  the  centres  are 
exaggerated,  the  phenomenon  of  Cheyne-Stokes  breathing  sets  in. 
The  pauses  depend  essentially  upon  the  depression  of  excitability 


XIII 


EESPIEATOEY  EHYTHM 


501 


below  the  threshold,  at  which  the  external  and  internal  stimuli 
are  inadequate  to  throw  the  central  organs  into  excitation ;  the 
groups  appear  when,  owing  to  rise  of  excitability,  the  external  and 
internal  stimuli  again  become  effective  (Luciani,  1879).  The 
same  theory  of  periodic  respiration  was  formulated  almost 
simultaneously  by  Eosenbach  (1880) ;  by  Sokolow  and  Luchsinger 


FIG.  236. — Oscillations  of  tone  in  respiratory  muscles  in  rabbit  poisoned  with  piridine.  (Mosso.) 
R,  respirations  recorded  with  a  Marey's  tambour  applied  to  xiphoid  process.  F,  tracing  of 
blood  pressure  in  carotid,  recorded  simultaneously  with  a  mercury  manometer.  The  pro- 
nounced oscillations  of  respiration  are  seen  not  to  be  associated  with  perceptible  altera- 
tions of  blood  pressure. 

(1880),  who  endeavoured  to  reinforce  it  by  ingenious  marshalling 
of  the  facts;  by  Langendorff  and  Siebert  (1881),  who  confirmed 
and  developed  the  work  of  their  predecessors ;  lastly,  by  A.  Mosso 
(1885),  who  resumed  and  consolidated  it  by  new  observations. 


Fio.  237.— Thoracic  respiration  in  sleep  of  robust  subject,  recorded  with  Marey's  pneumograph  ; 
shows  periodic  oscillations  of  both  inspiratory  and  expiratory  excursions.     (A.  Mosso.) 

Zuntz  (1882)  correctly  pointed  out  the  great  analogy  between 
the  classical  phenomenon  of  Cheyne-Stokes  respiration  and  the 
alternation  of  sleep  and  waking.  Sleep  corresponds  with  the 
pause,  the  waking  state  with  the  group.  Just  as  complete 
awakening  is  preceded  by  an  ascending  phase  of  waking  up, 
and  sleep  is  preceded  by  a  descending  phase  of  drowsiness,  so 
the  Cheyne-Stokes  phenomenon  shows  increase  and  decrease. 

VOL.  i  2  K  I 


502  PHYSIOLOGY  CHAP. 

Mosso  has  pointed  out  other  yet  more  convincing  analogies  from 
clinical  observation.  In  sleep  the  pupils  contract,  the  eyes  rotate 
inward  and  upward;  in  the  waking  state  the  pupils  dilate,  the 
eyes  rotate  outward  (Fontana).  Just  so  in  periodic  respiration,' 
when  the  pause  commences,  the  pupils  retract,  the  eyes  converge 
inwards  and  upwards;  when  the  group  commences,  the  pupil 
dilates,  the  eyes  look  forward  (Leube).  At  the  beginning  of  the 
pause  some  patients  are  drowsy  and  become  insensible  ;  ab  the 
beginning  of  the  group  they  are  restless,  and  again  suffer  pain 
(Leube,  Merkel).  Certain  subjects  close  their  eyes  at  the  termina- 
tion of  the  group,  at  the  commencement  of  the  pause,  and  in  the 
midst  of  it,  and  open  them  again  at  the  commencement  of  the 
group  or  soon  after  (Frantzel,  Hein,  Kaufmann).  In  more  serious 
cases  the  stupor  and  unconsciousness  are  continuous  throughout 
the  Cheyne- Stokes  breathing  ;  in  other  cases  consciousness 
returns,  partly  at  any  rate  during  the  groups ;  in  others,  lastly,  the 
respiratory  phenomenon  takes  place  in  the  awakening  state. 
These  are  differences  of  intensity,  shades  and  gradations  of  one 
fundamentally  identical  process,  which  explains  why  t.he  patient 
now  reacts  and  now  fails  to  respond  to  external  stimuli  during  the 
periodic  pause.  "  The  pause,"  writes  Mosso,  "  always  implies  a 
more  or  less  serious  drowsiness  of  the  nerve  centres,"  which  is  as 
much  to  say,  in  more  exact  and  strictly  physiological  language, 
that  during  the  pauses  the  respiratory  centres  suffer  a  negative 
variation  in  their  excitability.  Reflex  excitability,  automatic 
excitability,  or  reflex  and  automatic  excitability  together?  The 
answer  to  this  important  question  necessitates  some  consideration. 
Let  us  consider  the  extremes.  In  many  cases,  whether  clinical 
or  experimental,  of  periodic  respiration,  the  reflex  excitability  of 
the  centres  is  maintained.  Sometimes  it  is  sufficient  to  invite  the 
patient  to  breathe,  or  to  excite  him  with  acoustic,  luminous,  thermal 
or  painful  stimuli,  during  the  pause,  in  order  immediately  to  cut  it 
short,  and  obtain  respiratory  movements  (Biot,  Saloz,  Murri, 
Bordone).  In  rabbits  with  divided  bulb  which  breathe  periodically, 
faradisation  of  the  centres,  with  strong  and  infrequent  break 
shocks,  will  produce  respiratory  movements,  either  during  the 
groups  or  during  the  pauses  (Kronecker  and  Marckwald).  These 
facts  do  not,  as  some  maintain,  contradict  the  theory  that  periodic 
respiration  depends  essentially  upon  periodic  oscillations  in  the 
excitability  of  the  centres,  because  the  substitution  of  artificial  for 
natural  stimuli  probably  involves  disturbance  of  the  whole  of  the 
intimate  and  delicate  metabolic  process  on  which  the  periodic 
grouping  of  the  central  impulses  that  determine  Cheyne-Stokes 
respiration  depends ;  -but  it  has  certainly  been  demonstrated  that 
the  reflex  excitability  of  the  centres,  though  reduced,  is  not 
suspended,  during  the  pauses  in  these  cases.  Accordingly,  it  must 
be  assumed  that  the  periodic  quantitative  variation  in  the  external 


xiii  KESPIKATOKY  EHYTHM  503 

stimuli  acting  on  the  centres,  can  and  must  co-operate  with  the 
functional  intermittence  characteristic  of  these  centres,  owing  to 
the  alternations  of  groups  and  pauses. 

The  other  extreme  cases  of  periodic  respiration  are  the 
experiments  of  Sokolow  and  Luchsinger,  and  of  Langendorff  and 
Siebert  on  the  frog,  and  more  particularly  those  so  admirably 
carried  out  by  Fano  on  the  tortoise.  In  these  cases  the  reflex 
excitability  of  the  centres  (particularly  the  capacity  of  reacting  to 
the  stimulus  of  the  blood)  is  not  merely  lessened,  but  is  entirely 
suspended.  Here,  then,  periodic  respiration  is  a  more  simple 
phenomenon :  when  reflex  excitability  is  suspended,  the  automatic 
excitability  of  the  centres  dominates  the  stage  completely,  and  the 
grouping  of  the  respirations  is  the  external  expression  or  record  of 
the  special  mode  in  which  the  energy  accumulated  within  them — 
in  consequence  of  the  slow  processes  of  metabolism — is  liberated 
and  developed,  until  it  is  finally  exhausted.  The  importance  of 
the  facts  adduced  by  Fano  consists  not  in  any  refutation  of 
the  theory  formulated  by  us  in  1879,  which  is  left  untouched 
because  it  deals  with  an  essentially  distinct  order  of  phenomena ; 
but  in  its  demonstration  that  the  two  forms  of  excitability  with 
which  the  elements  of  the  respiratory  centres  are  endowed  do  not 
suffer  from  the  vicissitudes  of  metabolism  in  the  same  degree, 
since  in  poikilo thermic  animals,  under  certain  special  conditions, 
reflex  activity  may  be  entirely  suspended,  or  profoundly  depressed, 
while  automatic  excitability  persists  and  is  manifested  by  char- 
acteristic upward  and  downward  fluctuations. 

This  lengthy  chapter  has  been  exclusively  devoted  to  the 
nervous  factors  of  the  respiratory  mechanism.  But  a  further 
series  of  important  facts  shows  that  the  chemical  respiratory 
activity  of  the  tissues  is  also  dominated  by  the  nervous  system, 
which  may  excite  or  moderate  it,  and  even  cause  the  value  of  the 
respiratory  quotient,  i.e.  the  ratio  between  the  oxygen  absorbed 
and  the  carbonic  acid  given  off,  to  oscillate. 

We  shall  consider  this  interesting  subject,  which  exceeds  the 
limits  of  the  physiology  of  the  respiratory  apparatus,  in  due  time, 
along  with  the  metabolism,  or  material  exchanges,  of  the  body  as  a 
whole. 

BIBLIOGRAPHY 

The  following  monographs  and  memoirs  are  most  frequently  quoted  from  the 
copious  literature  of  this  subject : — 

FLOURENS.     Recherches   experimentales   sur   les   proprietes   et   les   fonctions  du 

system  e  nerveux.     Paris,  1842. 
BROWN-SEQUARD.     Journal  de  physiologie,  i.,  1858. 
M.  SCHIFF.     Lehrbuch  der  Physiol.,  1858-59.     Gesam.  Beitrage  zur  Physiol.,  i. 

Lausanne,  1894. 
ROSENTHAL.     Die  Atembewegungen  und   ihre   Beziehungen  rzum  Nervus  vagus. 

Berlin,  1892.     Hermann's  Handbuch  d.  Physiol.,  iv.     Leipzig,  1882. 
HERING  and  BREUER.     Sitzungsber.  d.  Wiener  Akademie,  Ivii.,  ii.,  1868. 


504  PHYSIOLOGY  CHAP,  xm 

PFLUGER.     Archiv  f.  d.  ges.  Physiol.,  i.,  1868. 

TRAUBE.     Gesammelte  Beitrage,  ii.     Berlin,  1871. 

EWALD.     Archiv  f.  d.  ges.  Physiol.,  vii.,  1873. 

GIERKE.     Archiv  f.  d.  ges.  Physiol.,  vii.,  1873. 

LUCIANI.     Lo  Sperimentale.     Firenze,  1879. 

SOKOLOW  and  LUCHSINGER.     Pfliiger's  Arch.,  xxiii.,  1880. 

LANGENDORFF  and  SIEBERT.     Du  Bois-Reymond's  Arch.  f.  Physiol.,  1881. 

GAD.     Du  Bois-Reymond's  Arch.  f.  Pysiol.,  1880-81-85-86. 

FANO.     Lo  Sperimentale.     Firenze,  1883-84-86. 

MIESCHER.     Du  Bois  Reymond's  Arch.  f.  Physiol.,  1885. 

Mosso.  R.  Accademia  dei  Lincei.  Roma,  1885.  Fisiologia  dell'  uomo  sulle  Alpi. 
Milano,  1898. 

ZUNTZ  and  GEPPERT.     Pfliiger's  Arch.,  xxxviii.,  1886. 

MARCKWALD.  Zeitschrift  fiir  Biologic,  1887.  (Contains  summary  of  publications 
to  that  date.) 

BORDONI.     Lo  Sperimentale.     Firenze,  1888. 

STEFANI  and  SIGHICELLI.     Lo  Sperimentale.     Firenze,  1888. 

ADUCCO.     Annali  di  freniatria  e  scienze  affini.     Torino,  1889. 

GAD  and  MARINESCO.     Du  Bois-Reymond's  Arch.,  1893. 

GIBSON,  G.  A.     Cheyne-Stokes  Respiration,  1882. 

LEWANDOWSKY.     Du  Bois-Reymond's  Arch.,  1896. 

FREDERICQ.     Arch.  d.  Biol.,  1900-1. 

NEANDER.     Skandin.  Arch.  f.  Physiol.,  ii.,  1902. 

BAGLIONI.  Centralbl.  f.  Physiol.,  1903.  Zur  Analyse  der  Reflexfunktion,  Wies- 
baden, 1907. 

BORUTTAU.     Ergebnisse  der  Physiol.,  i.  and  iii,,  2,  1902,  1904. 

N.  ZUNTZ,  A.  LOEWY,  F.  MULLER,  W.  CASPARI.  Hohenklima  und  Berg- 
wanderungen,  1906.  Bong  &  Co. 

Recent  English  Literature  :— 

W.  J.  GIES  and  S.  J.  MELTZER.     Studies  on  the  Influence  of  Artificial  Respiration 

upon   Strychnine   Spasms   and   Respiratory    Movements.       Amer.    Journ.    of 

Physiol.,  1903,  ix.  1-25. 
W.  E.  DIXON  and  T.  G.  BRODIE.     Contributions  to  the  Physiology  of  the  Lungs. 

Part  I.     The  Bronchial  Muscles,  their  Iimervation  and  the  Action  of  Drugs 

upon  them.     Journ.  of  Physiol.,  1903,  xxix.  97-173. 
I.    H.   HYDE.     Localisation   of   the   Respiratory   Centre   in  the   Skate.      Amer. 

Journ.  of  Physiol.,  1904,  x.  236-258. 
J.  S.  HALDANE  and  J.  G.  PRIESTLEY.     The  Regulation  of  the  Lung  Ventilation. 

Journ.  of  Physiol.,  1905,  xxxii.  225-266. 
I.  H.  HYDE.     A  Reflex   Respiratory  Centre.     Amer.    Journ.    of  Physiol.,   1906, 

xvi.  368-377. 
G.  N.  STEWART  and  F.  H.  PIKE.     Resuscitation  of  the   Respiratory  and  other 

Bulbar  Nervous  Mechanism  with  Special  Reference  to  the  Question  of  their 

Automaticity.     Amer.  Journ.  of  Physiol.,  1907,  xix.  328-359. 
G.  N.  STEWART  and  F.  H.   PIKE.     Further  Observations  on  the  Resuscitation  of 

the   Respiratory   Nervous   Mechanism.     Amer.    Journ.    of  Physiol.,    1907-8, 

xx.  61-73. 
G.    N.    STEWART.      Some    Observations    on    the    Behaviour    of   the    Automatic 

Respiratory  and  Cardiac  Mechanisms,  etc.     Amer.  Journ.  of  Physiol.,  1907-8, 

xx.  407-438. 
C.  G.  DOUGLAS  and  J.  S.  HALDANE.     The  Causes  of  Periodic  or  Cheyne-Stokes 

Breathing.     Journ.  of  Physiol. ,  1909,  xxxviii.  401-419.] 
C.    G.    DOUGLAS  and  J.    S.    HALDANE.     The   Regulation  of  Normal  Breathing. 

Journ.  of  Physiol.,  1909,  420-440. 


CHAPTER    XIV 

THE   LYMPH,    AND    INTERCHANGES    BETWEEN   THE   BLOOD    AND 
THE   TISSUES 

P*  CONTENTS.  —  1.  Structure  of  lymphatic  vascular  system,  lymph  spaces, 
sinuses  and  cavities.  2.  Origin ;  physical,  morphological  and  chemical  char- 
acteristics ;  qualitative  and  quantitative  variations  of  lymph.  3.  Lymphatic 
circulation,  and  the  various  mechanical  factors  by  which  it  is  determined. 

4.  Formation  of  lymph  from  the  blood  capillaries,  and  the  so-called  lymphagogues. 

5.  Secretory    theory    of    Heidenhain,     and    transudation    theory    of   Colmheim. 

6.  Formation  and  modification  of  lymph  by  the  tissues.     7.   Lymphoid   tissue, 
follicles    and    lymphatic    glands.     8.  Bone    marrow.     9.   The    thymus.     10.  The 
spleen.     Bibliography. 

No  less  important  than  the  gas  exchanges  between  the  blood 
and  the  tissues,  to  the  life  of  the  cells  of  which  the  latter  consist, 
is  the  exchange  of  solid  matters  in  which  the  blood  yields  to  the 
tissues  the  substances  necessary  to  their  nutrition  and  restoration 
(histogenic  substances),  and  the  tissues  yield  to  the  blood  the 
products  of  their  elaboration,  transformation,  or  consumption 
(histolytic  substances,  anabolic  and  katabolic.) 

The  nutritive,  like  the  respiratory,  exchanges  are  almost 
invariably  accomplished  by  means  of  the  lymph,  which  is  the  true 
internal  medium  in  which  the  elements  of  the  tissues  live. 
Hence  the  study  of  the  nutritive  exchanges  includes  the  study  of 
the  lymph ;  of  the  functions  of  the  lacunar  and  vascular  system 
which  contain  it ;  of  the  functions  of  the  tissues  and  organs  which 
more  particularly  contribute  to  its  formation  and  modifications ; 
of  the  mechanical  factors  that  are  constantly  setting  it  in  motion 
and  renewing  it,  driving  it  out  into  the  blood  torrent.  All  these 
will  be  discussed  in  the  present  chapter. 

I.  The  Lymphatic  System,  discovered  by  Aselli,  Pecquet, 
Kudbeck,  Bartholin,  in  the  first  half  of  the  seventeenth  century 
(see  Chap.  VI.  6),  is  one  of  the  most  extended  and  most  important 
in  the  body.  It  embraces,  not  only  the  vessels,  follicles,  and 
lymphatic  glands,  but  also  the  whole  of  the  connective  tissues, 
and  the  system  of  lacunae  or  interstitial  spaces  which  exist  in 
every  part  of  the  body,  particularly  where  there  are  more  or  less 
loosely  constituted  connective  tissues.  Even  the  large  serous 

505 


506 


PHYSIOLOGY 


CHAP. 


cavities,  such  as  the  peritoneum,  the  pleura,  the  pericardium,  the 
meninges,  and,  generally  speaking,  the  whole  of  the  serous  sheaths 
that  invest  the  organs,  form  part  of  the  lymphatic  system  in  the 
widest  sense  of  the  word. 

As  regards  the  morphological  questions,  many  of  them  very 
complicated  and  much  disputed,  that  arise  over  this  system,  we 
must  refer  to  treatises  on  anatomy  and  histology.  Here  we  can 
only  summarise  the  general  notions  that  are  most  intimately 
connected  with  physiological  problems. 

From  the  structural  point  of  view,  we  may  distinguish  in 
the  lymphatic  system  :  the  lymph  vessels  properly  so-called,  the 
lymphatic  capillaries,  the  parenchymatous  lymph  spaces,  the  large 
lymphatic  or  serous  cavities. 

(a)  The  lymphatic  vessels  constitute  a  rich  system  of  canals 


FIG.  238. — Supra  valvular  swelling  of.  lymphatic  in  cat's  mesentery,  treated  with  silver  nitrate. 
(Ranvier.)  The  smooth  muscular  fibres  which  surround  the  vessel  interlace  in  various 
directions  at  the  seat  of  the  swelling. 

which  are  very  similar  in  the  structure  of  their  walls  to  the  veins, 
and  like  them  are  richly  provided  with  valves,  which  open  centri- 
petally  and  close  in  a  centrifugal  direction.  These  are  specially 
abundant  in  the  small  lymphatic  vessels,  e.g.  in  those  of  the 
mesentery.  Above  each  valve  the  vessel  is  somewhat  dilated,  so 
that  when  there  are  many  valves  the  vessel  assumes  a  moniliform 
or  beaded  appearance.  The  muscle  cells  in  the  tunica  media  of 
the  vessel  walls  are  for  the  most  part  arranged  in  a  circular 
direction  ;  but  at  the  supra  valvular  points  of  dilation  they  run  in 
various  directions,  so  as  to  form  a  network  (Fig.  238).  Like  the 
blood-vessels,  the  lymphatics  lie  in  a  bed  of  connective  tissue,  and 
gradually  unite  into  vessels  which  become  increasingly  larger,  until 
they  finally  converge  (in  man  and  in  the  higher  vertebrates)  into 
two  principal  channels:  the  thoracic  duct,  which  opens  by  an 
orifice  provided  with  valves  into  the  left  subclavian  vein ;  and  the 
right  lymphatic  trunk,  which  opens  into  the  right  subclavian  vein. 
The  lymphatics  from  the  right  side  of  the  head  and  neck,  right  arm 


xiv  THE  LYMPH  507 

and  lung,  right  side  of  thorax,  and  heart,  and  part  of  the  upper 
surface  of  the  liver,  unite  in  the  right  lymphatic  trunk ;  all  the 
other  lymph  vessels,  including  those  which  come  from  the  intestines 
(known  as  lacteals,  because  during  the  absorption  of  the  digestive 
products  of  alimentation  they  conduct  the  chyle,  which  has  a  milky 
aspect),  lead  into  the  thoracic  duct. 

In  this  union  of  the  lymphatics  into  ever-widening  channels, 
their  diameter  does  not  increase  as  rapidly  as  that  of  the  veins : 
moreover,  they  often  form  plexuses  which  anastomose  among 
themselves ;  while,  lastly,  they  enter  all  along  their  course  into 
special  relations  with  the  so-called  lymphatic  glands  which,  from 
a  schematic  point  of  view,  may  be  considered  as  analogous  in 
structure  to  the  rete  mirabile  of  the  blood-vessels,  and  which  retard 
the  flow  of  the  lymph  along  the  vessels  that  conduct  it. 

(6)  The  lymph  capillaries  are  simpler  in  structure  than  the 
lymphatic   vessels  properly  so-called.     They  consist  of  a  simple 
membranous  coat,   the  exceedingly  delicate  structure   of  which 
when  stained  with  silver 
nitrate,  shows  flat  plates    _^ 
with  characteristic  wavy 
outlines  interlacing  one 
with  another  (Fig.  239). 
They  have  no  valves,  but      w^  ..„ 

are    usually    larger     in       ^O?a  /^  ^  ^>5^ 
calibre  than  the  smallest 

Of    the     lymphatics,    and     Fm.^  239.—  Epitheliokl  ^platelets  ^of  lymphatic  capillaries 


distinctly  larger  than  ^S^'8  intestine'  treated  with  8ilver  nitrate> 
the  blood  capillaries. 

They  are  irregular  in  form,  and  anastomose  among  themselves  so 
as  to  form  a  species  of  network,  with  uneven  meshes  and  very 
varied  form.  This  lymphatic  rete,  irregularly  excavated  from  the 
connective  tissue  which  supports  it,  opens  or  communicates  freely 
with  the  lymph  vessels,  which,  although  smaller  than  the 
capillaries,  have  a  more  regular  course,  are  clothed  with  fusiform 
epithelial  cells  of  less  sinuous  outline,  and  are  provided  with 
valves. 

To  form  a  clear  conception  of  the  difference  in  form,  arrange- 
ment, and  proportions  of  the  blood  and  the  lymphatic  capillary 
network,  Fig.  240,  in  which  the  two  capillary  retes  are  injected 
with  contrasting  stains,  may  be  studied. 

From  the  physiological  point  of  view  it  is  important  to  note 
the  special  relation  of  the  lymphatics  and  the  blood-vessels  in 
particular  parts  of  the  body,  e.g.  the  central  nervous  system,  the 
parenchyma  of  the  liver,  the  bone  tissues.  In  these  regions  the 
smallest  arterial  and  venous  blood-vessels  are  enveloped  with 
lymphatic  sheaths,  just  as  the  heart  is  invested  by  the  pericardium 
and  the  viscera  by  the  peritoneum  (perivascular  lymphatics,  Fig. 


508 


PHYSIOLOGY 


CHAP. 


241).  It  can  be  shown  by  the  method  of  double  staining  with 
silver  nitrate  and  carmine  that  there  is  a  perivascular  lymphatic 
space  between  the  peripheral  layer  of  the  sheath  and  that  which 
adheres  to  the  surface  of  the  blood-vessels ;  that  slender  connecting 
filaments  or  lamellae  pass  between  the  two  layers ;  that  the  wavy 
epithelioid  plaques  of  the  external  layer  are  continued  on  to  the 


FIG.  240.  —Frog's  interdigital  membrane,  with  injected  blood  and  lymph  vessels.  (Ranvier.) 
ss.  Network  of  blood  capillaries ;  II,  network  of  lymph  capillaries  ;  pp,  pigment  cells.  Mag- 
nification, 50  diameters.  >.£ 

internal  layer,  and  also  invest  the  connecting  lamellae.  Where 
the  blood-vessels  are  much  increased  in  size,  they  perforate  the 
lymphatic  sheath,  and  the  two  kinds  of  vessels  run  distinct  from, 
but  alongside,  one  another.  In  certain  of  the  lower  animals, 


FIG.  241. — (Left.)  Artery  of  frog's  mesentery,  enclosed  in  perivascular  lymphatic,  which  is 
stained  with  silver  nitrate,  to  show  the  outlines  of  epithelioid  cells.  (Klein.) 

Fio.  242. — (Right.)  Aorta  of  tortoise,  enclosed  in  large  perivascular  lymphatic.  (Gegenbaur.) 
Numerous  filaments  of  connective  tissue  are  seen,  connecting  the  blood-vessel  with  the 
lymphatic. 

however,  e.g.  in  the  frog,  the  larger  vessels  are  also  surrounded  by 
lymphatic  sheaths,  as  also  the  aorta  in  the  tortoise  (Figs.  241,  242). 
Kusconi  (1845)  was  the  first  to  describe  the  perivascular  lymphatic 
sheath. 

(c)  Outside  the  lymph  capillaries  also,  in  every  part  of  the 
body,  and  more  particularly  where  there  is  loose  connective  tissue, 
a  labyrinth  of  lacunae  or  interstices  of  the  most  varied  forms 


xiv  THE  LYMPH  509 

and  dimensions,  which  are  generally  known  as  lymphatic  spaces, 
because  they  are  full  of  lymph,  may  be  observed.  Again,  the 
tissues  devoid  of  blood-vessels,  like  the  cornea  and  the  cartilages, 
are  provided  with  minute  lacunar  canaliculi,  to  which  the 
lymphatic  humour  necessary  to  cell  nutrition  penetrates.  These 
parenchymatous  lymph  spaces  cannot  be  considered  as  lymph 
capillaries,  because  they  are  not  invested  with  the  characteristic 
epithelioid  lining,  which  forms  the  true  wall  of  the  latter.  They 
represent  a  diffuse  system  of  lacunae,  interstitial  to  the  cells 
of  the  various  tissues,  which,  according  to  Bichat's  doctrine,  is 
generally  regarded  as  the  origin  of  the  vascular  lymphatic  system, 
i.e.  of  that  provided  with  characteristic  walls.  In  many  inver- 
tebrates the  lacunar  system,  which  has  no  proper  wall,  is  the  only 
one  that  co-exists  with  the  blood  vascular  system  ;  so  that  we  may 
logically  regard  the  lymphatic  vascular  system  as  a  perfecting,  a 
canalisation  or  successive  centralising,  of  the  primary  lacunar  or 
interstitial  system  (Milne  Edwards). 

We  know  that  the  lymph  spaces  communicate  freely  with  the 
lymph  capillaries  properly  so-called,  because  a  fluid  stain  such  as 
Prussian  blue,  when  injected  into  the  meshes  of  the  subcutaneous 
connective  tissue  by  means  of  a  syringe,  penetrates  to  the  interior 
of  the  lymphatics,  particularly  if  the  oedematous  swelling  that 
forms  at  the  point  of  injection  is  compressed  by  the  finger,  so  as 
to  increase  the  tension  of  the  distended  lacunar  spaces  and  facilitate 
the  penetration  of  the  coloured  fluid  -by  the  natural  way  of  com- 
munication with  the  lymphatics. 

(d)  Besides  the  minute  parenchymatous  lymph  spaces  and 
sinuses,  the  lymphatic  capillaries  and  vessels  communicate  freely 
with  the  serous  cavity  of  the  peritoneum,  pleura,  pericardium, 
tunica  vaginalis  of  the  testicles,  sub-arachnoid  spaces,  chambers  of 
the  eye,  membranous  labyrinth  of  the  ear,  etc.  So  that  these 
larger  and  smaller  cavities,  which  normally  contain  lymphatic 
effusions,  are,  with  regard  to  the  system  of  lymphatic  vessels,  in  the 
same  relation  as  the  minute  parenchymatous  lymph  spaces.  The 
researches  of  Kecklinghausen,  of  Ludwig  and  Schweigger-Seydel, 
of  Dogiel,  of  Eanvier  and  others,  have  shown  this  theory,  as 
previously  enunciated  by  Mascagni,  to  be  correct.  It  is  easy  with 
Prussian  blue  to  inject  the  lymphatic  rete  of  the  centre  of  the 
diaphragm  in  a  rabbit  recently  killed  by  bleeding  and  hung  head 
downwards,  on  pouring  the  stain  into  the  abdominal  cavity  of  the 
diaphragm  and  assisting  its  penetration  to  the  lymphatic  rete  of 
the  tendinous  centre  by  means  of  artificial  respiration  with  the 
bellows  (Fig.  243).  On  treating  the  excised  diaphragm  of  a  rabbit 
with  silver  nitrate  (1  in  300),  the  impregnation  of  the  tendinous  tissue 
and  epithelioid  investment  of  the  two  faces,  pleural  and  peritoneal, 
reveals  its  structure  and  special  disposition.  On  the  pleural 
surface  the  system  of  lymphatic  vessels  is  shown  in  the  form  of 


510 


PHYSIOLOGY 


CHAP. 


arborisations  with  anastomosing  trunks,  the  extreme  branches  of 
which  form  parallel  canaliculi,  corresponding  to  intertendinous 
clefts  (Fig.  244). 

The  black  lines  of  intercellular  impregnation  are  clearer  and 
more  delicate  on  the  peritoneal  face  where  there  are  large  polygonal 
cells,  with  here  and  there  small  islands  of  lesser  and  rounded  cells  ; 
these  are  the  lymph  cells  which  invest  the  orifice  and  walls  of  the 
small  canals  that  bring  the  peritoneal  cavity  into  direct  communi- 
cation with  the  lymphatic  rete  of  the  tendinous  centre  (Fig.  245). 


Fio.  243.— Rabbit's  diaphragm,  viewed  from  abdominal  surface,  with  lymphatic  rete  injected  with 
Prussian  blue.     (C.  Ludwig  and  Schweigger-Seydel.)    The  figure  is  somewhat  reduced. 

According  to  Kanvier  there  is  no  need  to  invoke  the  existence  of 
intercellular  stomata  to  explain  the  ready  penetration  of  coloured 
fluids  or  solid  particles  from  the  peritoneal  cavity  to  the  lymphatic 
plexus,  since  the  small  cells  which  occupy  the  orifices  of  the  afore- 
said canaliculi  do  not  completely  occlude  them.  Still  the  retro- 
peritoneal  membrane  of  the  frog,  which  forms  the  wall  of  the 
cisterna  lymphatica  major  in  these  animals,  has,  according  to 
Schweigger-Seydel  and  Dogiel  and  Eanvier  himself,  true  stomata 
or  apertures  surrounded  by  epithelial  cells  which  are  somewhat 
differentiated  and  communicate  freely  with  the  peritoneal  cavity 
(Fig.  246). 


XIV 


THE  LYMPH 


511 


It  is  very  probable  that  there  is  direct  communication,  similar 
to  that  which  has  been  described  in  detail  for  the  peritoneal  cavity 
and  lymphatic  capillary  network  of  the  tendinous  centre  of  the 
diaphragm,  in  all  the  other  serous  cavities  of  the  body.  Bizzozero- 


FIG.  244. — Central  tendon  of  rabbit's  diaphragm  treated  with  silver  nitrate,  viewed  from  pleura!) 
surface.  (Ranvier.)  I,  I,  Lymphatic  vessels  in  form  of  clear  spaces  anastomosing  with  one 
another,  and  united  by  almost  parallel  inter-tendinous  clefts.  Magnification  of  20  diameters. 

and  Salvioli  described  the  communicating  canaliculi  between  the 
lymphatic  of  the  parietal  pleura  and  the  pleural  cavity. 

Other  writers  admit  free  communication,  in  the  form  of  small 


FIG.  245. — (Left.)  Central  tendon  of  rabbit's  diaphragm,  treated  with  silver  nitrate,  seen  from 
peritoneal  surface.  (Ranvier.)  /,  Inter-tendinous  lymphatic  clelt;  e,  epithelioid  investing 
cells,  forming  at  certain  places  along  the  lymph  canaliculae  islands  of  small,  somewhat 
granulated  cells,  which  surround  a  stonia  that  is  not  always  visible. 

FIG.  246.— (Right.)  Epithelioid  platelet  from  frog's  retroperitoneal  membrane,  treated  with  silver 
nitrate,  viewed  from  peritoneal  surface.  (Ranvier.)  I,  I,  Intercellular  lines  of  platelets  which 
surround  an  aperture  or  stonia  .communicating  with  lymphatic  canaliculi. 

pores  or  canaliculi,  with  the  lymphatic  rete  in  the  free  walls  of 
certain  mucosae,  such  as  the  bronchial  and  nasal  mucosa.  The 
interstitial  adenoid  tissue  of  the  lungs  is  rich  in  lymph  canals, 
which  form  a  large  irregular  lymphatic  meshwork  round  the 
bronchi,  pulmonary  lobules  and  blood-vessels.  When  animals  are 


512  PHYSIOLOGY 


CHAP. 


made  to  breathe  pigmented  fluids  by  means  of  a  spray,  the 
pigments  penetrate  by  tiny  pores  through  the  epithelial  cells  of 
the  mucosa  (Klein). 

This  theory  is  reinforced  by  the  extraordinary  rate  at  which 
fluids  and  also  blood  are  absorbed  when  injected  into  the  trachea 
of  living  animals.  Nothnagel  found  blood -corpuscles  in  the 
interstitial  lymph  spaces  of  the  lungs  barely  3-5  minutes  after 
injection. 

II.  The  lymph  contained  in  the  lymphatic  system,  as  briefly 
described  above,  comes  from  three  different  sources : — 

(a)  The  blood,  which,  by  the  network  of  blood  capillaries  to 
the  various  tissues,  constantly  pours  into  the  lymph  spaces  the 
materials  required  for  the  nutrition  of  the  tissue  cells. 

(ft)  The  living  elements  of  the  tissues,  which  continually  give 
off  to  the  same  system,  both  the  products  of  their  synthetic  or 
anabolic  processes,  destined  for  use  by  other  tissues  and  organs, 
and  the  products  of  their  analytic  or  katabolic  processes,  destined 
to  be  eliminated  from  the  body. 

(c)  The  food-stuffs  •  introduced,  and  more  or  less' modified  or 
digested  in  the  alimentary  canal,  known  as  a  whole  by  the  name 
of  chyle,  which  is  periodically  absorbed  by  the  lymphatic  roots  of 
the  intestinal  villi.  On  the  strength  of  this  threefold  origin  we 
may  theoretically  distinguish  between  blood  lymph,  tissue  lymph, 
and  lymph  of  the  digestive  apparatus  or  chyle.  Leaving  aside  for 
the  moment  the  chyle,  the  formation  and  absorption  of  which  will 
be  discussed  elsewhere,  we  will  consider  the  constituents  of  lymph 
properly  so-called  (of  the  blood  and  tissues),  which  is  constantly 
being  formed  and  poured  out  into  the  lymphatic  lacunar  spaces. 
Since  the  demand  for  nutritive  materials  in  the  different  tissues 
and  organs  is  quantitatively  and  qualitatively  very  different,  and 
since,  on  the  other  hand,  each  tissue  and  organ  is  the  seat  of 
specific  anabolic  and  katabolic  processes,  it  follows  necessarily  that 
the  lymph  in  the  lacunar  system  of  the  different  organs  must 
differ  in  consistency  and  composition. 

Up  to  the  present,  however,  we  possess  very  few  analytical 
data  in  regard  to  the  differences  presented  by  the  lymph  coming 
from  the  different  organs,  nearly  all  these  differences  being  much 
attenuated,  or  even  obliterated,  in  the  lymph  collected  from  the 
larger  vessels,  into  which  alone  it  is  possible  to  introduce  a 
cannula.  In  examining  the  general  characters  and  chemical 
composition  of  lymph,  it  is  almost  always  collected,  as  it  flows, 
from  a  cannula  introduced  into  the  thoracic  duct  of  a  fasting  dog, 
which  yields  the  whole  of  the  chemical  constituents  from  tl 
several  lymphs  (coming  by  the  lymphatic  channels  to  the  different 
tissues  of  the  organs)  that  have  not  been  consumed  by  the  tissues, 
nor  absorbed  by  the  blood-vessels.  In  collecting  lymph  from 
animals  of  small  bulk  (rabbits,  cats,  etc.)  the  thoracic  fistul 


xiv  THE  LYMPH  513 

(direct  method)  may  be  replaced  by  an  indirect  method,  i.e.  the 
fistula  of  the  jugular  or,  as  Jappelli  advises,  of  the  subclavian. 

The  lymph  which  flows  from  the  fistula  of  the  thoracic  duct  is 
a  watery,  slightly  opalescent  fluid,  with  a  specific  weight  of  1012- 
1022,  less  viscous  than  blood;  when  left  to  itself  it  coagulates 
slowly,  forming  a  more  tenuous  and  less  copious  fibrin  reticulum 
than  that  which  forms  in  the  blood.  A  small  quantity  of  peptone 
injected  into  the  veins  makes  it  incoagulable,  although  the  blood 
remains  coagulable  (Shore). 

When  examined  under  the  microscope  it  presents  a  certain 
number  of  leucocytes  precisely  similar  to  those  of  the  blood, 
varying  in  size  from  5  /x  to  10  /x.  The  smaller  and  younger 
leucocytes  predominate  in  the  lymph,  the  larger  and  adult 
specimens  in  the  blood;  but  the  total  quantity  contained  in 
1  c.rnm.  of  lymph,  though  it  varies  considerably  in  different 
animals  and  in  the  same  animal  under  different  circumstances, 
seems  not  far  removed  from  that  of  the  leucocytes  in  the  blood. 

A  certain  number  of  erythrocytes  are  also  constantly  present 
in  lymph,  even  when  precautions  are  taken  to  avoid  any  admixture 
with  blood,  or  when  the  lymph  which  is  moving  through  the 
lymphatics  of  a  living  animal  is  examined.  The  lymph  being 
almost  or  wholly  deprived  of  oxygen,  the  erythrocytes  give  a 
brownish  colour  to  the  fluid ;  but  on  contact  with  air,  owing  to 
the  transformation  of  the  haemoglobin  into  oxyhaemoglobin,  they 
assume  a  clear  red  hue,  which  tinges  "the  surface  of  the  clot.  It 
is  probable  that  some  of  these  are  not  formed  locally,  but  come 
by  diapedesis  from  the  blood  capillaries.  So  far  as  is  known 
at  present  there  are  no  blood-platelets  in  lymph  (Chap.  IV.  9, 
p.  118). 

The  plasma  ot  lymph  contains  all  the  essential  constituents  of 
blood  plasma ;  but  the  quantitative  relations  are  a  little  different. 
In  particular  it  has  been  pointed  out  that  lymph  plasma,  as 
compared  with  that  of  blood,  is  poor  in  protein,  which  has  been 
partly  absorbed  by  the  tissues ;  on  the  other  hand,  it  is  richer  in 
water  and  alkaline  salts,  so  that  its  reaction  is  generally  more 
alkaline  than  that  of  blood  plasma.  For  the  rest,  the  chemical 
composition  of  lymph  varies  considerably.  According  to  the  most 
reliable  of  the  existing  analyses,  the  percentage  quantity  of  water 
varies  from  93'5-95'S ;  the  total  solid  residue  is  much  less  than 
that  of  blood,  varying  from  4*2-6'5 ;  the  protein  varies  from  3*5- 
4'3,  fibrin  from  0'04-0'06  ;  generally  speaking,  the  protein  content 
diminishes  owing  to  the  muscular  movements,  and  increases  in 
proportion  with  rest  and  sleep.  The  neutral  fats,  soaps,  cholesterin 
and  lecithin  are  scanty  in  lymph  (0'4-0'9  per  cent);  when  it 
sometimes  looks  turbid  and  highly  opalescent  this  is  due  not  to 
fats  but  to  protein  compounds  in  a  special  state  of  aggregation. 
It  also  contains  a  small  quantity  of  sugar  (dextrose).  Some 

VOL.  I  2  L 


514  PHYSIOLOGY  CHAP, 

observers  have  also  found  a  considerable  amount  of  urea.  The 
ash  of  lymph,  like  that  of  blood  serum,  oscillates  from  07-0 '8  per 
cent,  and  contains  an  excessive  amount  of  sodium  chloride,  from 
the  lymph  flowing  from  the  thoracic  duct  in  dog.  Hammarsteii 
was  unable  to  extract  more  than  traces  of  oxygen  and  37-53  per 
cent  of  carbonic  acid,  i.e.  a  quantity  greater  than  that  contained 
in  arterial  and  less  than  that  which  can  be  extracted  from  venous 
blood. 

This  last  fact  shows  that  part  of  the  carbonic  acid  developed 
by  the  tissues  is  directly  absorbed  by  the  blood  capillaries  and 
veins,  both  in  the  lymph  spaces  and  in  the  lymph  capillaries.  So, 
too,  we  must  remember  that  many  of  the  solid  products  of  the 
tissues  are  directly  absorbed  by  the  blood-vessels,  and  that  the 
lymph  contains  only  such  substances  turned  out  by  the  blood  as 
are  not  taken  up  by  the  tissues  (blood-lymph)  and  such  products 
of  the  tissues  as  are  not  directly  absorbed  by  the  blood-vessels 
(tissue-lymph).  The  lymph  spaces  and  capillaries  thus  represent 
an  internal  medium  in  which  the  reciprocal  exchange  of  materials 
between  blood  and  tissues  takes  place  ;  and  the  lymph  vessels, 
properly  so-called,  represent  a  drainage  system  which  slowly,  by 
long  and  circuitous  paths,  reconducts  all  the  residual  matters,  both 
from  blood-  and  tissue-lymph,  left  over  from  the  direct  exchanges 
in  the  lymph  spaces  and  capillaries,  to  the  circulatory  torrent.  In 
view  of  this  it  is  evident  that  the  quantity  of  lymph  that  flows 
through  the  thoracic  duct  in  the  time-unit  cannot  be  taken  as  a 
measure  of  the  total  amount  of  lymph  poured  into  the  blood  day 
by  day.  According  to  Heidenhain,  the  average  amount  of  lymph 
flowing  in  24  hours  from  the  thoracic  duct  of  a  dog  that  weighs 
10  kgrms.  is  about  640  c.c.  Noel  Paton,  from  the  thoracic  duct  of 
a  patient  who  weighed  60  kgrms.,  obtained  about  1  c.c.  of  lymph 
per  minute,  i.e.  1440  c.c.  in  24  hours.  From  a  woman,  Munk  and 
Eosenstein  obtained  a  quantity  varying  between  1200  and  2280 
c.c.  per  diem. 

It  is  possible  also  to  collect  lymph  from  different  parts  of  the 
body  by  introducing  a  small  cannula  into  the  larger  lymphatic 
trunks  of  the  upper  and  lower  limbs,  the  liver,  and  the  intestine. 
The  lymph  from  the  limbs  is  similar  to  that  flowing  from  the 
thoracic  duct  of  a  fasting  animal,  but  it  contains  a  smaller  amount 
of  solids  (2-4  per  cent).  On  the  other  hand,  the  lymph  from  the 
liver  contains  more  solids  (6-7  per  cent),  even  in  the  fasting 
animal.  That  coming  from  the  intestine  during  inanition  exhibits 
an  amount  of  solids  intermediate  to  the  above.  For  the  rest,  both 
the  composition  and  the  quantity  of  these  various  lymphs  differ 
considerably  according  to  circumstances,  especially  in  regard  to 
the  degree  of  functional  activity  in  the  tissues  and  organs  whence 
they  are  taken. 

The   large   serous  cavities  of    the   peritoneum,   pleura,   peri- 


xiv  THE  LYMPH  515 

€ardium,  tuiiica  vaginalis  of  testicles,  etc.,  normally  contain  only 
a  small  quantity  of  lymphatic  effusion,  sufficient  to  lubricate 
the  walls.  But  under  abnormal  conditions,  particularly  with 
mechanical  obstruction  of  the  venous  circulation,  and  with  marked 
delay  in  the  circulation,  however  produced,  it  is  possible  to  collect 
large  quantities  of  fluid  from  these  cavities,  which  differs  con- 
siderably in  composition  from  the  lymph  obtained  from  the 
thoracic  duct.  It  has  a  low  specific  gravity  (1008-1015) ;  contains 
a  minimum  amount  of  proteins  (2'2-7'3  per  cent) ;  is  almost 
free  of  corpuscles  :  does  not,  generally  speaking,  coagulate  spon- 
taneously, but  since  it  contains  fibrinogen,  coagulates  on  the  addi- 
tion of  thrombin,  or  fluids  which  contain  it  (see  Chap.  V.  6). 

Bainbridge,  Asher,  Mendel  and  Hooker  noted  that,  under 
given  experimental  conditions,  the  flow  of  lymph  from  the 
cannula  inserted  in  the  thoracic  duct  continues  for  a  not 
inconsiderable  time  after  death.  Jappelli  and  D'  Errico  have 
recently  demonstrated  that  a  post-mortem  flow  of  lymph  occurs 
in  every  case,  but  is  especially  persistent  when  the  death  of 
the  animal  occurs  instantaneously  (electrocution)  and  without 
haemorrhage.  According  to  the  same  authors  small  quantities  of 
post-mortem  lymph  are  constantly  obtained  from  the  cervical  and 
brachial  trunks  as  well.  It  is,  however,  mainly,  though  not 
exclusively,  visceral  in  origin. 

Post-mortem  lymph  differs  essentially  in  its  characteristics  from 
the  normal  by  : — 

(a)  Its  osmotic  pressure,  which  gradually  increases  up  to  and 
beyond  that  of  normal  blood  ; 

(V)  Its  gradually  decreasing  electrical  conductivity  ; 

(c)  Its  increased  viscosity  and  greater  content  of  solids  ; 

(d)  Peculiar  changes  in  the  velocity  of  outflow ; 

(e)  Its  appearance,  now  more  haematoid,  now  more   chylous, 
always  more  turbid. 

These  researches  of  D'  Errico  and  Jappelli  show  plainly  that 
post-mortem  lymph  is  not  pre-formed  lymph.  Hence  it  becomes 
necessary  to  admit  that  the  processes  of  lymphagenesis,  whatever 
these  may  be,  continue  for  some  time  after  death.  Nor  should 
this  be  surprising  when  we  reflect  that  after  somatic  death  there 
is  no  instantaneous  abolition  of  all  the  haemodynaniic,  osmotic, 
cellular,  and  other  factors  which  are  invoked  in  explaining  the 
formation  of  lymph  in  the  living  animal. 

III.  The  lymph  contained  in  the  lymphatic  system  is  in 
continual  movement  from  the  roots  to  the  large  trunks,  like  the 
blood  in  the  veins  into  which  these  empty  themselves.  This  is 
proved  by  the  fact  that  ligation  of  a  lymphatic  trunk  produces 
filling  and  swelling  below  and  comparative  evacuation  above,  as 
in  the  veins ;  and  that  the  valves  in  the  lymphatics  as  in 
the .  veins  impede  the  centrifugal  course  of  the  fluids  within 


516  PHYSIOLOGY  CHAP, 

them.  With  direct  microscopic  observation  of  the  mesenteric 
lymphatics  of  small  mammals,  again,  it  is  possible  to  follow  the 
slow  centripetal  movements  of  the  lymph  by  the  motion  of  tl>e 
leucocytes  which  it  contains. 

In  this  movement  of  the  lymph,  as  in  the  analogous  case  of 
the  blood,  we  have  to  determine  the  mechanical  factors  by  which 
it  is  produced,  its  velocity  and  pressure,  and  its  variations  under 
given  conditions. 

It  is  a  fact  that  the  lymphatic  vessels  are  under  a  certain 
degree  of  tension,  i.e.  they  support  a  certain  amount  of  pressure 
which  dilates  them  (Ludwig  and  Noll).  In  a  lymphatic  of  the 
horse's  neck,  the  pressure  is  10-20  mm.  of  water  (Weiss). 
Since  fluids  moving  in  a  tube  always  proceed  from  higher  to  lower 
pressure,  we  must  assume  (even  if  it  cannot  be  directly  proved) 
that  the  pressure  is  maximal  at  the  roots  of  the  lymphatics ;  that 
it  gradually  falls  from  the  branches  to  the  lymphatic  vessels ;  that, 
lastly,  it  is  minimal  at  the  point  at  which  the  thoracic  duct  opens 
into  the  left  subckvian,  and  the  right  lymphatic  trunk  into 
the  right  subclavian.  A  priori  the  velocity  of  movement  of 
the  lymph  should  decrease  from  the  greater  trunks  to  the  more 
peripheral  branches  in  proportion  as  the  area  of  the  current- 
bed  widens.  Experimentally,  however,  it  is  found  that  even  in 
the  larger  lymphatic  vessels,  e.g.  the  lymphatic  trunk  of  the 
horse's  neck,  the  velocity  of  movement  is  very  low ;  according  to 
Weiss  it  equals  250-300  mm.  per  minute. 

What  is  the  origin  of  the  vis  a  tergo  which  produces  the 
centripetal  movement  of  the  lymph,  and  is  sufficient  in  man  to- 
overcome  the  force  of  gravity  from  the  extreme  end  of  the  lower 
limbs  to  the  height  of  the  venous  vessels  of  the  neck  ?  In  the  frog 
and  other  amphibia,  reptiles  and  fishes,  the  lymph  hearts  which 
beat  rhythmically,  and  which,  by  their  muscular  structure  and 
function,  present  many  analogies  with  the  blood  heart,  are 
undoubtedly  of  great  importance  to  the  lymph  flow.  The  frog  is 
provided  with  four  lymph  hearts :  the  two  (posterior)  sacral  hearts 
situated  at  the  sides  of  the  coccyx,  being  covered  only  by  a  delicate 
aponeurosis  and  by  the  skin,  can  be  seen  beating  even  before  they 
are  dissected  ;  the  two  (anterior)  axillary  hearts  are  covered  by  the 
scapula.  The  sacral  hearts  carry  away  the  lymph  from  the 
lymphatics  that  accompany  the  sciatic  vein  ;  the  axillary  hearts 
that  of  the  vessels  coming  from  the  head  and  anterior  limbs. 
In  other  amphibia,  reptiles  and  fishes,  there  are  only  two  lymph 
hearts.  Without  entering  into  their  mode  of  functioning,  we 
can  see  that  since  the  frog  is  poorly  provided  with  regular 
lymphatic  vessels,  and  in  compensation  has  a  copious  supply  of 
large  sinuses  and  lymph  sacs,  the  four  hearts  represent  so  many 
pumps  necessary  for  promoting  the  flow  of  lymph  from  the  said 
sacs  and  sinuses. 


XIV 


THE  LYMPH 


517 


I! 


There  are  no  lymph  hearts  in  man  and  other  mammals  ;  the 
walls  of  the  lymph  vessels  are,  however,  provided  (as  above  stated) 
with   muscular   elements,  which   interlace   above  the   valves   in 
various    directions    (Fig.    238)   in    such    a          c<s 
manner   as  to  suggest   that   they   may,  by  „ 

their  rhythmical  contraction,  function  as 
minute  hearts  (Foster).  No  direct  observa- 
tions exist  to  confirm  this  theory.  On  the 
other  hand,  there  are  certain  data  which 
in'dicate  that  some  of  the  lymphatic  vessels, 
under  given  conditions, are  capable  of  rhythm- 
ical and  peristaltic  contractions  and  dilata- 
tions in  the  direction  of  the  current.  Arnold 
Heller  observed  under  the  microscope,  in  the 
mesentery  of  a  guinea-pig  anaesthetised  with 
chloral  hydrate,  that  the  lymphatics  succes- 
sively contracted  and  relaxed  (on  an  average 
six  times  a  minute)  in  the  peristaltic  direc- 
tion from  the  periphery  to  the  centre.  This 
observation  is  unsupported,  and,  generally 
speaking,  it  must  be  held  that  the  muscle  cells 
of  the  lymphatic  walls  behave  passively,  like 
those  of  the  blood-vessels,  in  regard  to  the 
normal  lymph  current. 

Pursuing  the  line  of  strict  analogy  be- 
tween blood-vessels  and  lymphatics,  it  may 
also  be  stated  that  the  muscle  cells  of  the 
lymphatics  have  an  automatically  oscillating 
tonus,  which  may  be  modified  or  regulated 
by  the  influence  of  special  vascular  nerves. 
The  recent  work  of  Gley  and  Camus  (1894- 
1895)  has  made  it  possible,  in  the  physiology 
of  the  lymphatic  vessels,  to  define  accurately 
certain  fundamental  ideas  as  to  the  dilator 
and  constrictor  functions  of  the  nerves  which 
influence  the  muscle  cells  of  the  receptaculum 
chyli  and  the  thoracic  duct.  After  success- 
fully overcoming  some  serious  technical  diffi- 
culties, these  two  experimenters  succeeded 
in  registering  on  dogs  the  pressure  in  the 
receptaculum,  when  reduced  to  a  closed 
cavity,  communicating  below  by  a  cannula 

with  a  receiver  filled  with  physiological  saline,  kept  at  low  and 
constant  pressure ;  above,  it  communicated  by  a  second  cannula 
inserted  into  the  thoracic  duct  with  a  small  water  manometer, 
provided  with  a  float  and  a  lever  writing  on  a  smoked  cylinder. 
Fig.  247  gives  a  clear  idea  of  the  method. 

VOL.  I  2  L  a 


If 
Is 


eg 


518  PHYSIOLOGY 


CHAP. 


The  results  arrived  at  by  Gley  and  Camus  can  be  summed  up 
in  a  few  words  : — 

(a)  The  left  splanchnic  nerve  contains  dilator  fibres  and  also 
constrictor  fibres  to  the  receptaculum.     As  the  electrical  excitation 
of  the  nerve  trunk  almost  always  produces  depressor  effects,  we 
must   conclude   either   that  the   constrictor  fibres   are  not  very 
numerous  in  the  part  of  the  nerve  which  is  stimulated,  or  that 
they  are  much  less  excitable  than  the  dilator  fibres. 

(b)  The  motor  nerves  to  the  thoracic  duct  run  in  the  thoracic 
part  of  the  sympathetic  chain.     Here  also  there  are  dilator  and 
constrictor  fibres,  and  the  activity  of  the  former  outweighs  that  of 
the  latter. 

(c)  It  is  also  possible,  retiexly,  by  exciting  a  sensory  nerve  to 
determine    dilator    effects   upon   the   receptaculum   and   thoracic 
duct.     If,  e.g.,  one  sciatic  is  ligatured,  alternate  constriction  and 
dilatation  will  be  observed  in  place  of  the  former  constant  tonus. 
On  exciting  the  central  end  of  a  divided  sciatic,  there  is  invariably 
a  dilator  effect..    On   the  other   hand,   asphyxia    on  cessation  of 
artificial  respiration  determines  contraction  of  the  thoracic  duct 
similar  to  that  exhibited  by  the    stomach,  bladder,  uterus,  bile 
duct,  etc. 

These  observations  show  the  importance  of  the  muscle  cells 
and  motor  nerves  of  the  lymphatic  vessels,  in  so  far  as  they  are 
capable  of  altering  their  lumen,  and  can  thus  facilitate  or  hinder  the 
centripetal  movement  of  the  lymph.  If  these  active  vascular 
movements  were  more  energetic,  rhythmical,  and  peristaltic  or 
progressive  from  the  branches  to  the  lymphatic  trunks,  it  is 
evident — in  view  of  the  function  of  the  many  valves  with  which 
the  lymphatic  system  is  furnished — that  they  would  have  the 
same  effect  as  the  heart-beats,  and  would  represent  a  form  of 
propulsion  adequate  to  account  for  the  lymphatic  circulation. 
But  this  view  has  no  experimental  basis,  nor  does  it  harmonise 
with  the  theory  of  the  venous  circulation,  which  depends  essentially 
upon  the  vis  a  tergo  developed  by  the  cardiac  rhythm. 

According  to  Ludwig  the  lymphatic  circulation  depends 
essentially  on  the  vis  a  tergo  due  to  the  pressure  on  the  lymph 
that  fills  the  pareuchymatous  lymph  spaces,  which  in  its  turn 
depends  on  the  pressure  under  which  the  blood  circulates  in  the 
capillaries.  Thus  the  lymph  circulation  is  also,  in  last  resort,  the 
effect  of  the  force  of  the  heart.  The  lymph  represents  a  transudate 
from  the  blood  through  the  fine  membrane  constituted  by  the 
capillary  walls,  by  a  process  of  filtration  which  depends  on  the 
difference  of  pressure  between  the  blood  circulating  in  the 
capillaries  and  the  lymph  poured  out  into  the  spaces.  This  theory 
will  be  analysed  below.  For  the  moment  it  is  enough  to  say  that 
it  is  correct,  in  so  far  as  it  assumes  the  lymph  circulation  to  be 
due  to  the  vis  a  tergo  caused  by  the  pressure  on  the  lymph  in  the 


xiv  THE  LYMPH  519 

lacunar  system ;  but  it  is  inadequate,  in  so  far  as  it  holds  the  lymph 
to  be  merely  a  product  of  simple  nitration.  The  pumping  of  the 
heart  promotes  the  flow  of  lymph,  not  merely  by  favouring 
filtration  through  the  capillaries,  but  by  another  simpler  mechanism. 
At  each  systolic  efflux  the  whole  arterial  tree  is  dilated  by  the 
passage  of  the  pulse  wave,  in  consequence  of  which  the  whole  of 
the  perivascular  lymphatics  immediately  receive  an  impulse  to 
centripetal  evacuation  of  the  lymph  which  they  contain.  Since 
it  is  shown  from  plethysmographic  observations  that  the  total 
volume  of  the  body  is  increased  at  each  beat  transmitted  from  the 
heart,  it  may  logically  be  admitted  that  the  lymphatics  which  run 
separate  from,  and  independent  of,  the  blood-vessels  must,  at  each 
pulsation  of  the  arteries,  be  sensible  of  a  pressor  effect  which 
favours  the  movement  of  the  lymph. 

More  important,  however,  and  certainly  better  demonstrated, 
is  the  influence  exerted  on  the  lymph  circulation  by  the  active 
and  passive  movements  of  the  skeletal  muscles.  If  a  cannula  is 
introduced  into  the  principal  lymphatic  vessel  from  the  lower 
extremity  of  a  large  dog,  no  flow  of  lymph  will  be  perceived  so 
long  as  the  muscles  of  the  limb  are  relaxed  and  motionless.  As 
soon,  however,  as  active  movements  are  excited  in  the  limb,  or 
alternate  passive  movements  of  flexion  and  extension  are  performed 
on  it,  the  flow  of  lymph  through  the  cannula  becomes  suddenly 
active.  This  fact  shows  that  the  muscular  movements  compress 
the  lymphatics  and  empty  them  in  the  centripetal  direction, 
because  the  valves  prevent  movement  of  the  lymph,  as  of  venous 
blood,  in  a  centrifugal  direction.  The  rise  of  the  lymph  in  the 
lower  limbs  is  principally  effected  by  this  mechanism. 

On  the  other  hand,  the  respiratory  mechanism  exerts  a 
preponderating  influence  on  the  movements  of  the  lymph  in  the 
visceral  lymphatics.  The  lymphatic,  like  the  venous,  current  is 
continuously  affected  by  the  normally  negative  pressure  of  the 
thorax,  by  which  the  lymph  is  aspirated,  like  the  venous  blood, 
from  the  extrathoracic  to  the  intrathoracic  vessels.  This  negative 
thoracic  pressure  increases  during  inspiration,  and  the  positive 
abdominal  pressure  increases  during  active  expiration.  These 
two  factors  accelerate  the  flow  of  lymph,  particularly  in  the 
visceral  lymphatics  and  thoracic  duct,  and  propel  it  to  the 
mouths  of  the  two  subclavian  veins,  where  it  mixes  with  the  venous 
blood. 

IV.  The  exact  determination  of  the  mechanism  which  effects 
the  formation  of  lymph  is  one  of  the  most  complex  problems 
in  physiology,  and  has  been  much  .discussed  of  late  years  since 
Heidenhaiii  (1891)  opposed  to  the  mechanical  theory  of  filtration 
(a  relic  of  the  ancient  doctrine  of  Bartholin  and  Mascagni,  to 
which  Ludwig  and  his  School  endeavoured  to  give  an  experimental 
basis)  his  secretory  theory,  in  which  he  asserts  that  the  formation 

VOL.  I  2  L  I 


520  PHYSIOLOGY  CHAP. 

of  lymph  is  essentially  the  effect  of  the  activity  of  the  living 
cells  which  form  the  walls  of  the  blood  capillaries.  For  better 
orientation  in  this  difficult  and  complex  subject  we  will  tabulate 
the  different  groups  of  facts  brought  forward  and  consider  them 
separately. 

A  consensus  of  experimental  results  shows  that  increased 
pressure  in  the  blood  capillaries  is  followed  by  increased  formation 
of  lymph  :— 

(a)  We    know   from    the   works   of   Emminghaus    that    the 
occlusion  of  the  veins  in  one  limb  not  only  increases  the  current 
flowing  through  the  cannula  inserted  into  the  lymphatic  of  that 
limb,  but  considerably  modifies  the  constitution  of  the  lymph,  so 
that   it  becomes  richer  in  erythrocytes  and  poorer  in  dissolved 
solids.     This  fact  is  in  agreement  with  clinical  observation,  which 
shows  that  in  cardiac  failure,  hepatic  cirrhosis,  thrombosis  of  the 
veins,  and  in  fact  in  every  case  in  which  there  is  obstruction  or 
local   interruption    to   the   venous    circulation,   with    consequent 
increase  of  pressure  in  the  capillaries,  the  lymph  transudes  through 
these  so  freely  that  oedema,  i.e.  stagnation  or  accumulation  of 
lymph  in  the  tissue  spaces,  results. 

(b)  Both  Heidenhain  and  Starling  obtained  the  same  results 
as  Emminghaus  after  ligaturing  the  portal  vein  in  the  dog.     The 
marked  rise  of  intra-capillary  pressure  in  the  intestine  increased 
the  flow  of  lymph  from  the  cannula  in  the  thoracic  duct  four  to 
five  times,  with  diminution  of  colloids  and  increase  of  red  blood- 
corpuscles. 

(c)  On  obstructing  the  vena  cava  inferior  above  the  diaphragm 
there  is  a  marked  fall  of  arterial  pressure,  in  consequence  of  which 
the  viscera  become  anaemic,  while  there  is  still  an  acceleration  of 
lymph-flow  greater  than  that  which  occurs  after  ligation  of  the 
portal    vein.      The   lymph   does    not   contain   more   blood,   but 
becomes   richer   in   solids,  while  at    the  same  time  clearer   and 
less  coagulable.     These  results  of  Heidenhain  were  controlled  by 
Starling,  who  demonstrated  that  in  the  above  experiments  the 
lymph  was  derived  from  the  lymphatics  of  the  liver  and  not  of  the 
intestines,  as  Heidenhain  believed.     In  fact,  after  the  occlusion  of 
the  vena  cava,  pressure  increased  below  the  point  where  the  block 
occurred,  producing  a  corresponding  rise  of  pressure  in  the  hepatic 
capillaries ;  on  the  other  hand,  the  pressure  in  the  portal  vein 
diminished  (as  known  by  the  blanching  of  the  intestines)  in  conse- 
quence of  the  marked  fall  of  aortic  pressure. 

(d)  On  occluding  the  thoracic  aorta  (by  introducing  from  the 
right  carotid  a  catheter  ending  in  a  rubber  balloon  which  could 
be  inflated  by  the  injection  of  water),  Heidenhain  observed  that 
arterial  pressure  below  the  point  obstructed  could  fall  to  zero, 
while  the  lymph  current  might  continue  for  1  to  2  hours  longer, 
although    with   diminished   velocity   and    progressive    reduction. 


xiv  THE  LYMPH  521 

The  composition  of  the  lymph  also  changed,  since  it  became  turbid  .    j 

and  whitish,  not  from  increase  in   the  fats  and  leucocytes,  but  /   / 

owing  to  a  kind  of  partial  precipitation  of  the  proteins.     This 

turbidity  does  not  always  persist ;  sometimes  it  ceases  after  15  to 

30  minutes.     In  any  case  the  percentage  content  of  solids  in  the 

lymph  increases,  even  after  it  has  become  clear.    Lastly,  the  lymph, 

while   of    greater   density,   becomes  less   coagulable   during   the 

occlusion  of  the  aorta.     On  repeating  this  experiment  Starling 

saw  that  the  pressure  in  the  inferior  vena  cava  is  not  altered,  and 

may  even  rise  slightly  under  the  conditions  described,  while  that  in 

the  aortic  system  is  greatly  reduced.     The  lymph  that  continues 

to  flow  after  the  occlusion  of  the  aorta  can  therefore  only  come 

from  the  lymphatics  of  the  liver.     Indeed,  on  ligaturing  the  latter, 

he  found  that  the  entire  ilow  of  lymph  from  the  thoracic  duct  was 

arrested. 

According  to  Heidenhain  these  phenomena  cannot  all  be 
interpreted  on  the  mechanical  theory  of  nitration ;  according  to 
Starling,  on  the  other  hand,  since  they  demonstrate  that  the 
increase  of  lymph  flow  is  invariably  associated  with  a  correspond- 
ing increase  of  pressure  in  certain  capillary  regions,  they  ar& 
cogent  arguments  for  the  importance  of  nitration  in  the  formation 
of  lymph.  The  various  changes  in  constitution  arid  concentration 
presented -by  the  lymph  from  the  different  regions  have  still, 
however,  to  be  explained. 

It  will  be  observed  that  in  all  the  •experiments  referred  to,  the 
increase  of  pressure  in  the  blood  capillaries  is  due  to  a  block  in 
the  venous  circulation,  which  is  accompanied  either  by  abnormal 
retardation  or  by  venous  stasis.  This  fact  never  occurs  under 
physiological  conditions.  It  may  be  conjectured  that  the  walls  of 
the  blood-vessels  are  altered  by  the  long  stagnation  of  the  venous 
blood,  that  they  become  more  permeable,  more  sensitive  to  changes 
in  pressor  effects,  and  permit  an  abnormal  nitration  of  lymph,  to 
which  they  do  not  lend  themselves  under  normal  conditions.  We 
cannot,  therefore,  from  these  facts  deduce  a  physiological  theory  of 
the  normal  formation  of  lymph  by  a  process  of  simple  filtration. 
Physiologically,  capillary  pressure  only  varies  in  consequence  of 
slow  oscillations  in  tone  of  the  small  arteries,  which  are  provided 
with  strong  muscles.  When  these  dilate,  capillary  pressure  rises,. 
because,  owing  to  diminished  resistance,  a  larger  amount  of  the 
impulsive  force  of  the  heart  is  transmitted  to  the  capillaries ;  but, 
in  addition  to  the  rise  of  pressure,  the  velocity  of  circulation 
through  the  capillary  network  rises  also,  so  that  its  walls  are 
bathed  in  a  blood  that  undergoes  rapid  and  constant  renewal.  In 
order  to  establish  the  significance  of  filtration  in  the  formation  of 
lymph  under  physiological  conditions,  it  must  also  be  shown  that  a 
simple  rise  in  arterial  and  capillary  pressure,  with  unimpeded 
venous  flow,  constantly  produces  increase  in  the  lymphatic 


522  PHYSIOLOGY  CHAP. 

current.  The  following  are  the  facts  which  bear  upon  this  pro- 
position : — 

(a)  When  in  a  dog  all  the  cervical  and  brachial  nerves  to  an 
anterior  limb  are  divided  so  as  to  paralyse  all  motor  nerves  to  the 
muscles  as  well  as  the  vessels,  and  the  cervical  cord  is  stimulated 
electrically  so  as  to  produce  contraction  of  all  the  vessels  of  the 
body  except  those  of  this  limb,  there  is  necessarily  a  marked  efflux 
•of  blood  with  increased  arterial  and  capillary  pressure  in  all  the 
vessels  of  the  paralysed  limb.  Nevertheless  the  quantity  of  lymph 
flowing  with  the  aid  of  the  passive,  rhythmical  movements  of  the 
limb  from  the  cannula  inserted  into  its  lymphatic  trunk  does  not 
show  the  slightest  augmentation,  but  rather  tends  to  diminish 
gradually,  as  it  did  previous  to  stimulation  of  the  spinal  cord 
(Ludwig  and  Paschutin). 

(6)  When  the  so-called  chorda  tympani  is  excited  there  is  a 
conspicuous  dilatation  of  the  small  arteries  of  the  submaxillary 
gland,  associated  with  increase  of  pressure  and  acceleration  of 
the  blood-flow  through  the  capillaries  (Chap.  X.  1,  p.  341).  These 
effects  are  certainly  associated  with  increased  formation  of  lymph, 
which  pours  into  the  glandular  lymphatic  spaces,  and  (as  we 
shall  see,  Vol.  II.  Chap.  II.)  is  immediately  utilised  by  the  gland 
cells  for  the  formation  of  an  abundant  salivary  secretion 
(Ludwig),  so  that  it  does  not  accumulate  in  the  glandular 
lymphatics.  If,  before  exciting  the  chorda  tympani,  the  animal  is 
slightly  atropinised,  the  vessels  of  the  gland  will  equally  dilate, 
and  capillary  pressure  rises  as  before ;  but  the  salivary  secretion 
does  not  occur,  nor  is  there  any  increased  formation  of  lymph, 
since  it  does  not  accumulate  in  the  connective- tissue  spaces  of  the 
gland,  nor  does  the  flow  of  lymph  from  the  glandular  lymphatics 
increase  (Heidenhain).  To  interpret  this  effect  we  must  remember 
that  atropine  paralyses  the  activity  of  the  secretory  nerves,  leaving 
the  vasodilator  fibres  of  the  chorda  tympani  untouched.  Mere 
arterial  dilatation  and  rise  of  pressure  and  circulatory  velocity  in 
the  capillaries  of  the  gland  are  not  enough  to  provoke  increased 
formation  of  lymph,  such  as  does,  on  the  other  hand,  occur 
when  the  secretory  activity  of  the  gland  cells  are  excited. 

These  facts  are  obviously  irreconcilable  with  the  theory  that  a 
primary  importance  must  be  assigned  to  the  mechanical  process  of 
filtration  in  the  physiological  formation  of  lymph.  They  prove 
that  when  the  increased  pressure  in  the  blood  capillaries  is 
associated  with  acceleration,  instead  of  with  slowing  or  stasis  of 
the  circulatory  current,  no  increased  formation  of  lymph  takes 
place. 

Another  important  series  of  experimental  observations  shows 
that  the  lymph  current  may  increase  conspicuously,  independent 
of  any  marked  rise  in  pressure  in  the  blood  capillaries  :— 

(a)  Certain  chemical  substances,  when  injected  into  the  blood, 


XIV 


THE  LYMPH  523 


induce  a  considerable  increase  in  the  formation  of  lymph,  and 
were  therefore  termed  lymphagogues  by  Heidenhain.  Such  are 
commercial  peptone,  extracts  of  crab's  muscle,  of  the  head  or  body 
of  leeches,  the  body  of  river  mussels,  the  intestine  or  liver  of  dog, 
egg  albumin,  curare,  and  (according  to  D'  Errico)  gelatin.  All 
these  substances  produce  the  same  effect  as  regards  flow  of  lymph 
from  the  thoracic  duct :  immediately  after  the  injection  of  the 
lymphagogue  into  the  vein,  the  lymph  current  increases  as  much 
as  four  times,  and  the  effect  may  last  for  over  an  hour.  The 
lymph  becomes  richer  in  proteins ;  it  subsequently  becomes  turbid, 
then  clears  again :  its  coagulability  diminishes  or  disappears. 
This  increase  in  the  lymphatic  current  coincides  with  a  slight  fall 
of  arterial  pressure,  associated  with  acceleration  of  cardiac  rhythm. 
Starling  holds  that  under  these  conditions  also  the  lymph  derives 
principally  from  the  liver,  and  is  therefore  more  concentrated  ;  and 
that  if  the  portal  lymphatics  are  ligatured  there  is  no  longer  any 
lymphagogic  action  after  injection.  Pugliese,  however,  has  shown 
that  extract  of  crab's  muscle  and  curare  produce  a  marked  increase 
of  lymph  in  the  front  limb  of  the  dog  as  well,  with  a  sensible 
increase  in  its  content  of  solids.  Increased  lymph  formation 
cannot  therefore  be  considered  as  a  phenomenon  localised  in 
the  hepatic  capillaries. 

(&)  As  against  these  lymphagogues  which  increase  the  lymph 
that  is  derived  from  the  Uood  Heidenhain  ranges  a  second  class  of 
substances,  which  are  lymphagogues  *  because  they  increase  the 
lymph  that  comes  from  the  tissues.  Such  are  sugar,  urea,  sodium 
chloride,  and  other  crystalloid  substances  when  injected  in 
sufficient  quantities  into  the  blood.  They  soon  leave  the  blood, 
abstracting  large  quantities  of  water  from  the  tissues,  which  is 
partly  reabsorbed  by  the  blood,  partly  goes  to  swell  the  lymphatic 
current.  The  flow  is  accelerated ;  the  lymph  becomes  momentarily 
turbid,  and  is  reddish ;  presently  it  coagulates  slowly,  although  it 
contains  many  crystalloids ;  it  is  conspicuously  poor  in  colloids. 
The  composition  of  the  blood  changes  in  consequence ;  the  water 
increases,  and  the  relative  quantity  of  erythrocytes  and  haemo- 
globin is  lessened.  The  increase  in  the  lymph  stream  is  usually 
associated  with  a  slight  rise  of  arterial  pressure,  proportionate  in 
each  case  to  the  quantity  of  lymph  produced. 

The  lymphagogues  of  the  second  series  accordingly  produce 
changes  in  the  blood  and  lymph  of  an  opposite  character  to  those 
observed  with  lymphagogues  of  the  first  series.  Their  antagonistic 
action  is  also  shown  by  the  fact  that  the  latter  do  not  excite 
urinary  secretion,  while  the  former  do,,  so  that  the  acceleration  of 
the  lymph  stream  is  parallel  to  the  excretion  of  urine. 

V.  These  facts,  as  demonstrated  by  Heidenhain,  were  confirmed 
by  successive  experimenters ;  but  they  have  given  rise  to  various 
interpretations.  Heidenhain  made  them  the  basis  of  his  secretory 


524  PHYSIOLOGY  CHAP. 

theory.  Cohnheim  had  already  on  several  occasions  expressed  the 
idea  that  the  vessel  walls  must  be  something  more  than  a  simple 
passive  filter.  Following  out  this  idea,  Heidenhain  affirmed  that 
the  lymphagogic  effects  of  the  double  series  of  substances  above 
indicated  should  be  considered  as  proving  that  the  epithelioid 
cells  which  constitute  the  walls  of  the  blood  capillaries  are  to  be 
considered  as  secretory  cells  analogous  to  gland  cells,  capable,  i.e., 
of  separating  certain  substances  from  the  blood,  and  of  pouring 
them  into  the  system  of  lymph  spaces  with  a  brisk  displacement 
of  water,  to  provide  for  the  various  and  specific  nutritive  needs  of 
the  different  tissues  and  organs.  Heidenhain  alleges  that  certain 
secretory  organs,  such  as  the  udder  of  the  milch  cow,  are  capable 
of  yielding  25  litres  of  milkier  diem,  containing  42 '5  grms.  of  lime. 
Since  the  lymph  poured  into  the  thoracic  duct  does  not  contain 
more  than  O1S  per  thousand  grams,  236  litres  of  lymph  would 
be  required  to  provide  the  gland  cells  with  all  the  lime  needed  for 
the  production  of  the  milk,  on  the  hypothesis  that  they  derive  all 
the  materials  required  for  their  function  from  the  lymph  as  such. 
If,  on  the  other  hand,  we  assume  secretory  activity  on  the  part  of 
the  cells  forming  the  capillary  walls,  it  is  easy  to  explain  how,  with 
slight  translocation  of  water,  they  are  able  to  supply  the  gland  with 
all  the  material  required.  Seeing  that  each  organ  or  tissue  must 
obtain  its  specific  nutritive  materials  from  the  lymph,  it  is  assumed 
that  they  pour  out  specific  products  into  the  lymph,  which  excite 
the  secretory  activity  of  the  capillary  walls,  and  thus  provoke 
secretion  of  those  substances  which  the  organ  requires. 

It  cannot  be  denied  that  this  theory  of  Heidenhain  is  a  very 
bold  one.  Not  because  (as  one  of  our  younger  physiologists  main- 
tains) it  diverges  from  the  principle  of  the  mechanical  interpretation 
of  functional  processes — the  admission  of  one  secretion  within  the 
body  more  or  less  could  not  sensibly  modify  the  general  trend 
of  science ;  but  because  Heidenhain,  prior  to  formulating  his 
secretory  theory,  did  not  examine  fundamentally  to  what  point 
the  process  of  lymph  formation  could  be  interpreted  by  the  aid  of 
the  physical  laws  at  present  known  to  us. 

To  the  secretory  theory,  W.  Cohnstein,  in  a  series  of  interest- 
ing papers  (1893-1896),  opposes  what  he  terms  the  transudation 
theory,  according  to  which  the  formation  of  lymph  is  due  to  two 
well-determined  physical  processes :  filtration,  which  depends  on 
the  difference  of  pressure  between  the  two  liquids  separated  by  a 
permeable  membrane,  represented  by  the  capillary  walls ;  and 
diffusion,  due  to  the  different  chemical  constitution  of  the  two 
fluids.  The  lymph  contained  in  the  extra  -  capillary  lymph 
spaces  is  during  life  the  subject  of  continuous  changes,  pro- 
duced by  the  metabolic  activity  of  the  parenchymal  cells,  which 
draw  from  it  the  substances  required  for  their  nutrition,  and 
pour  out  the  progressive  and  retrogressive  products  of  their 


xiv  THE  LYMPH  525 

elaboration.  Accordingly,  chemical  differences  between  the  lymph 
and  the  blood  plasma  of  the  capillaries  are  constantly  arising,  and 
promote  a  continuous  diffusion  current  from  the  blood  to  the 
lymph.  In  the  above  example  of  the  mammary  gland  it  is  con- 
ceivable that  its  secretory  epithelia,  by  constantly  subtracting 
lime  from  the  lymph,  set  up  a  persistent  diffusion  current,  by 
which  fresh  lime  passes  continually  from  the  blood  to  the  lymph 
by  way  of  the  capillary  walls.  That  this  diffusion  current  may 
be  rapid  enough  to  provide  for  the  chemical  needs  of  the  several 
tissues  will  be  readily  understood  on  considering  the  extra- 
ordinary rapidity  of  respiratory  gas  exchanges,  arterial  being 
transformed  into  venous  blood  in  the  time  during  which  the 
capillaries  are  traversed.  Cohnstein  also  quotes  the  researches  of 
v.  Brasol  (1884)  and  of  Klikowicz  (1886),  which  prove  that  sugar 
and  salts  injected  into  the  blood  in  concentrated  solutions  pass  in 
a  few  moments  from  the  blood  to  the  tissues,  and  thence  drive  out 
into  the  blood  such  quantities  of  fluid  as  considerably  to  increase 
the  blood  pressure  and  diminish  the  relative  quantity  of  haemo- 
globin from  30-60  per  cent.  These  facts  show  that  simple  processes 
of  diffusion  in  the  body  can  sufficiently  account  for  the  rapid 
transport  of  considerable  quantities  of  solid  matters  from  the 
blood  to  the  tissues.  Undoubtedly  the  same  may  occur  in  the 
normal  formation  of  lymph  when  diffusion  is  aided  by  filtration. 

There  .is  no  necessity  to  resort  to  any  mechanism  other  than 
that  of  diffusion  and  filtration  to  explain  the  effects  of  the 
lymphagogues  of  Heidenhain's  second  category.  Since  these 
increase  the  concentration  of  the  blood,  much  water  passes  from 
the  tissues  into  the  blood  to  re-establish  iso-tonicity,  or  equilibrium 
of  osmotic  pressure,  which  raises  the  pressure  in  the  capillaries  and 
favours  filtration,  and  therewith  the  lymph  stream,  along  with 
which  the  injected  substance  passes  out  of  the  blood.  Heidenhain 
observed  that  the  lymphagogic  action  of  crystalloids  was  pro- 
portional to  their  power  of  attracting  water,  which  again,  accord- 
ing to  v.  Limbeck,  is  proportional  to  their  diuretic  action. 

More  controversy  arises  as  to  the  interpretation  of  the  effects 
of  lymphagogues  of  the  first  category.  Since  the  increase  in  the 
lymph  current  cannot  be  explained  by  a  rise  in  intra-capillary 
pressure,  which,  on  the  contrary,  falls,  Starling  holds  that  these 
substances,  which  are  toxic  to  the  heart,  muscles,  and  leucocytes, 
are  also  toxic  to  the  epithelioid  cells  of  the  capillary  walls,  by 
chemically  -altering  them  and  rendering  them  more  permeable,  so 
that  the  normal  pressure  is  sufficient  to  cause  increased  filtration. 
Cohnstein,  on  the  other  hand,  maintains  that  the  lymphagogic 
action  of  these  substances  must  be  interpreted  as  the  effect  of 
diminution  of  the  endosmotic  equivalent  of  the  blood,  and  conse- 
quent diminution  in  the  quantity  of  water  that  passes  by  diffusion 
from  .the  lymph  spaces  into  the  blood  capillaries.  We  know  that 


526  PHYSIOLOGY 


CHAP. 


peptone,  extract  of  crab's  muscle,  etc.,  alter  the  composition  of  the 
blood,  making  it  more  permeable  and  rendering  it  incoagulable ; 
but  Cohnstein  has  demonstrated  experimentally  that  it  undergoes 
such  modifications  in  its  chemical  constitution  as  to  reduce  its 
endosuiotic  equivalent  very  considerably,  this  being  the  reason 
why  the  amount  of  lymph  increases,  and  with  it  the  lymphatic 
current. 

The  doctrine  of  transudation  (which  results  from  a  combina- 
tion of  the  process  of  nitration  with  that  of  diffusion)  is  thus 
adequate  to  explain  all  the  phenomena  of  the  formation  of  lymph 
under  various  experimental  conditions,  and  to  render  the 
hypothesis  of  the  secretory  functions  of  the  capillary  cells  super- 
fluous. .  Of  course  this  theory  does  not  exclude  the  possibility  that 
these  cells  may  under  abnormal  conditions  suffer  chemical  or 
physical  changes  which  induce  modifications  in  the  normal  forma- 
tion of  lymph,  since  both  nitration  and  diffusion  are  known  to 
depend  upon  the  constitution  of  the  permeable  animal  membranes. 
In  a  word,  it  is  not  denied  that  the  living  cells  of  the  capillary 
walls  are  the  seat  of  incessant  changes  corresponding  with  the 
degree  and  kind  of  their  metabolism.  What  is  denied,  as  being 
superfluous  and  non-proven,  is  that  they  fulfil  a  secretory  function 
properly  so-called,  and  that  the  substances  secreted  from  the  blood 
in  the  lymphatic  spaces  differ  specifically  according  to  the  specific 
needs  of  the  several  tissues  and  organs. 

The  latest  work  on  this  subject  by  Lazarus  Barlow,  Hamburger, 
and  Asher  tends  to  show  that  the  role  of  filtration  in  lympha- 
genesis  must  be  less  than  that  of  the  osmotic  processes  (diffusion), 
while  the  relative  permeability  of  the  cells  of  the  individual  tissues 
is  undoubtedly  of  importance  (Ellinger).  Asher  and  his  pupils,  in 
particular,  have  studied  the  influence  of  the  activity  of  cell 
metabolism  in  the  several  tissues  on  the  formation  of  lymph. 

Another  series  of  experimental  observations,  made  recently  by 
Carlson,  Greer,  and  Luckhardt  (1907-10),  is  of  some  interest  in  the 
problem  of  the  mechanism  of  lymph  formation.  Here  we  can 
only  state  briefly  that  in  a  large  number  of  experiments  (seventeen 
horses  and  five  dogs)  the  chloride  content  of  the  lymph  was  found 
higher  than  that  of  the  blood  serum ;  this  statement  is  confirmed 
by  the  fact  that  lymph  is  a  better  electrical  conductor  than  serum. 
A  ten  per  cent  increase  in  the  NaCl  content  of  a  physiological 
saline  solution  causes  an  increase  in  the  electrical  conductivity 
which  is  comparable  to  the  increased  conductivity  of  the  lymph 
over  the  serum  (Luckhardt).  These  facts  do  not  agree  with  any 
mechanical  theory  of  lymph  formation,  whether  the  filtration  or 
the  osmosis  theory.  According  to  the  former,  the  quantitative 
salt  content  of  both  lymph  and  serum  ought  to  be  the  same ; 
according  to  the  latter  it  ought  to  be  maintained  constant. 

Pugliese  (1901)  investigated  the  influence  of  the  vasomotor 


xiv  THE  LYMPH  527 

centres  on  the  formation  of  lymph.  On  cutting  the  medulla 
oblongata,  or  blocking  its  blood -supply  in  dogs  by  means  of 
artificial  emboli,  he  noted  a  rise  in  the  amount,  and  fall  in  the 
concentration,  of  the  lymph  flowing  from  the  thoracic  duct.  Under 
these  conditions,  also,  the  intravenous  injection  of  curare,  bile,  and 
urea  determined  an  increase  of  lymph,  which  with  the  two  first 
substances  becomes  more  concentrated,  with  urea,  on  the  contrary, 
less  concentrated  than  the  normal.  Peptone  in  dogs  with  a 
paralysed  vasomotor  centre  exhibits  a  much  less  intense  lympha- 
gogic  action  than  the  normal.  The  lymphagogic  action  of  caffein 
disappears  entirely,  while  sodium  chloride  preserves  its  action  of 
lymphagogic  potency. 

VI.  All  that  we  have  been  considering  refers  exclusively  to 
what  Heidenhain  calls  blood-lymph.  We  must  now  examine  the  so- 
called  tissue-lymph,  and  the  organs  which  more  particularly  concur 
in  forming  and  modifying  it. 

We  have  seen  that  lymph  cannot  be  considered  as  a  simple 
residue  of  blood  plasma,  unappropriated  by  the  tissue  cells.  Part, 
at  least,  of  the  chemical  products  formed  by  these  cells  is  poured 
into  the  lymph  spaces,  and  modifies  and  renders  more  complex 
the  lymph  turned  out  of  the  blood  capillaries.  Theoretically,  it  is 
undeniable  that  the  lymph  from  different  organs  and  tissues  must 
have  a  different  composition.  The  work  of  Heidenhain,  completed 
and  partly  rectified  by  Starling,  gives  confirmatory  evidence  of 
this.  The  lymph  coming  from  the  limbs  regularly  contains  a 
lower  percentage  of  proteins  than  that  from  the  intestine,  and  the 
latter  contains  a  larger  amount  of  proteins  than  that  from  the 
liver.  It  appears  improbable  that  this  difference  depends — as 
supposed  by  Starling — on  the  normal  differences  in  permeability 
of  the  blood  capillaries  in  different  areas.  It  is  more  logical  to 
admit  that  the  three  kinds  of  lymphs  are  dissimilar  because,  coming 
from  different  tissues,  they  are  modified  in  various  ways  by  the 
elaboration  products  of  the  same. 

The  quantity  of  lymph,  again — as  was  justly  observed  by 
Asher  and  Barbera — may  and  must  depend  on  the  degree  of 
functional  activity  of  the  tissue  cells.  When  the  work  of  an  organ 
increases,  the  quantity  of  dissimilation  products  increases  also,  and 
with  it  the  quantity  of  lymph  poured  into  the  lymphatic  spaces ; 
on  the  other  hand,  this  increase  in  the  products  eliminated  by  the 
organ  may,  since  it  modifies  the  difference  in  osmotic  pressure 
between  blood  and  lymph,  determine  an  increase  in  the  transudation 
of  plasma  through  the  blood  capillaries.  Experimental  data  in 
support  of  this  theory  are  not  wanting.  Stimulation  of  the  lingual 
branch  of  the  trigeminus  causes  a  marked  accumulation  of  lymph, 
with  consequent  oedema  in  the  corresponding  half  of  the  tongue. 
This  phenomenon  was  first  observed  by  Ostroumoff,  and  was 
subsequently  confirmed  and  developed  by  Marcacci  (1883).  It  i& 


528  PHYSIOLOGY  CHAP. 

only  necessary  to  tetanise  the  lingual  nerves  for  a  long  time,  and 
with  brief  interruptions,  in  order  to  produce  conspicuous  tumefac- 
tion of  the  half  of  the  tongue  corresponding  to  the  side  stimulated, 
associated  with  dilatation  of  the  arterial  and  venous  vessels. 
Marcacci  has  shown  that  the  effect  depends  principally  upon  the 
pronounced  formation  and  accumulation  of  lymph  (oedema),  rather 
than  on  hyperaemia.  After  protracted  tetanisation  of  the  lingual 
nerve,  he  saw  not  only  that  the  lymphatics  of  the  tongue  dilated, 
but  also  that  a  large  lymphatic  gland  which  is  in  direct  relation 
with  them,  and  lies  near  the  submaxillary  gland,  swelled  and 
increased  in  weight.  Since,  as  has  been  seen,  the  rise  of  arterial 
pressure  is  not  of  itself  enough  to  determine  any  great  increase  of 
filtration  through  the  capillaries,  we  hold  that  the  effect  depends 
on  the  extension  of  nerve  influence  in  this  case  to  the  lymph- 
forming  elements  of  the  lingual  tissue,  which,  when  excited,  pour 
a  more  copious  flow  of  lymph  into  the  lymphatic  spaces.  The  same 
thing  is  seen  on  exciting  the  chorda  tympani,  which  innervates  the 
submaxillary  gland,  but  with  the  difference  that  in  this  case  the 
lymph  which  is  more  abundantly  formed  does  not,  after  transform- 
ation into  the  saliva  of  the  glandular  cells,  flow  back  into  the 
lymphatic  system,  but  is  canalised  in  the  excretory  ducts  of  the 
gland. 

All  tissues  that  are  in  relation  with  the  lymphatic  system  are 
more  or  less  lymphagenic  in 'a  wide  sense,  i.e.  they  pour  into  the 
lymphatic  system  and  thence  into  the  blood  system  a  part  at  least 
of  their  elaboration  or  waste  products,  thereby  contributing  to  the 
formation  of  the  lymph  or  modification  of  its  composition.  Among 
these,  more  particularly,  are  the  so-called  lymphoid  tissues  in 
general,  the  follicles  and  glands  attached  to  the  lymphatics,  the 
red  bone-marrow,  the  thymus,  and  the  spleen. 

VII.  Lymphoid  (or  Adenoid)  Tissue  is  the  name  given  to  such 
tissues  as  consist  essentially  of  branching  cells  and  fibres  of 
connective  tissue  which  are  so  interconnected  as  to  constitute  a 
network  with  very  fine  meshes,  within  which  the  leucocytes  are 
enclosed  in  great  numbers.  Diffuse  in  form,  with  no  circumscribed 
boundaries,  the  lymphoid  tissue  is  found  in  the  mucosa  of  the 
respiratory  passages,  throughout  the  intestinal  tract,  in  the  marrow 
of  bones,  etc.  In  the  sharply-defined  form  of  rounded  nodules  the 
size  of  a  small  pin's  head,  lymphoid  tissue  appears  in  the  so-called 
solitary  follicles,  which  are  found  in  large  numbers  in  the  intestinal 
mucosa,  especially  in  its  lower  part.  Each  follicle  consists  of  an 
adenoid  rete,  with  very  fine  and  regular  meshes,  filled  with  leuco- 
cytes. The  meshes  are  larger,  and  the  leucocytes  less  crowded,  at 
the  centre  and  periphery  of  the  nodule,  as  shown  in  Fig.  248.  At 
the  surface,  where  the  follicle  projects  into  the  intestine,  the  villi 
are  usually  absent,  and  the  crypts  of  Lieberkuhn  are  found  at  its 
-circumference.  One  or  more  arterioles  penetrate  into  the  nodule, 


XIV 


THE  LYMPH 


529 


and  break  up  into  a  capillary  network  which  subsequently  reforms 
into  one  or  more  venules.  Kound  the  nodule  there  is  a  space  or 
lymphatic  sinus  filled  with  lymph,  interrupted  by  afferent  and 
efferent  blood-vessels  and  filaments  of  connective  tissue,  which 
unite  the  tissue  of  the  adenoid  serosa  with  the  surrounding 
connective  tissue.  The  lymph  sinus  and  the  blood-vessels  and 
connective-tissue  bridges  are  clothed  with  epithelioid  plates,  as 
shown  by  the  silver  nitrate  reaction. 

The  leucocytes  implanted  in  the  adenoid  rete  are  usually 
smaller  than  those  of  the  blood,  owing  to  the  paucity  of  protoplasm 
around  the  nucleus.  Many  of  them,  lying  within  the  central 


PIG.  2-18. — Solitary  follicle  from  large  intestine  of  man.     (Bnhm.)    ep,  Intestinal  epithelium  ; 
pi,  Lieberkiihn's  crypt ;  eg,  germinal  centre  ;  sm,  sub-mucous  tissue. 

mass  of  the  follicle,  are  in  the  stage  of  mitotic  division,  so  that 
Flemming  gave  the  name  of  centrum  germinativum  to  the  mid- 
point of  the  follicle,  at  which  there  is  a  continuous  multiplication 
of  leucocytes.  In  proportion  as  new  leucocytes  are  formed  at  the 
centre,  the  adult  leucocytes  which  lie  at  the  peripheral  part  of 
the  follicle  are  driven  towards  the  lymphatic  sinus,  where  they 
are  caught  up  in  the  general  lymph  current.  The  vis  a  tergo  that 
drives  them  out  of  the  meshes  of  the  adenoid  rete  is  no  doubt 
due  to  the  lymph  which  transudes  from  the  network  of  the 
blood  capillaries  in  the  follicle,  and  increases  the  tissue  tension. 
The  lymph  which  is  thus  formed,  while  it  serves  as  food  for  the 
leucocytes,  is  modified  by  the  products  of  their  metabolism.  It  is 
probable  that  a  proportion  of  these  products  passes  by  diffusion 
into  the  interior  of  the  blood-vessels,  so  that  the  blood,  on 
VOL.  I  2  M 


530  PHYSIOLOGY  CHAP. 

traversing  the  follicles,  yields  up  some  materials  and  acquires 
others. 

The  so-called  Peyer's  Patches,  of  an  oblong  oval  form,  which 
are  found  to  the  number  of  20-30  in  the  small  intestine  (particu- 
larly in  the  ileum),  consist  of  groups  of  the  solitary  follicles,  so 
that  they  are  also  termed  agminated  follicles.  Each  patch  in  man 
consists  of  50-100  follicles,  arranged  in  one  plane,  which  lie 
immediately  beneath  the  intestinal  epithelium,  and  dip  down  so 
far  into  the  submucosa  that  they  interrupt  the  muscular  layer. 
From  the  physiological  standpoint  they  differ  in  no  essential  from 
the  solitary  follicles. 

A  more  complex  structure  attaches  to  the  lymphatic  glands, 
numerous  and  widely  distributed  bodies  which  lie  along  the 


FIG.  249. — Vertical  section  of  dog's  lymphatic  gland,  the  afferent  lymphatics  injected  with  Prussian 
blue,  stained  with  picrocarmine.  (Klein.)  c,  Capsule,  showing  a  lymph  vessel  cut  trans- 
versely, communicating  with  cortical  sinuses  ;  a,  lymph  follicles  of  cortex  surrounded  by  lymph 
sinuses,  and  separated  by  trabeculae ;  b,  medullary  portion  of  gland,  showing'  reticular 
adenoid  tissue  and  lymphatic  sinuses  injected  with  blue.  Magnification  of  25  diameters. 

course  of  the  lymphatic  vessels.  They  differ  in  size,  and  are  for 
the  most  part  bean-shaped  or  kidney- shaped,  with  a  concavity 
which  is  called  the  hilum  of  the  lymphatic  gland,  whence  issue 
the  efferent  lymphatics,  while  the  afferent  vessels  enter  on  the 
convex  side.  The  arterial  and  venous  blood  -  vessels  enter  and 
leave  respectively  at  the  hilum.  Each  ganglion  is  invested  with 
a  capsule  composed  of  two  layers,  the  outer  of  which  consists  of 
loose  connective  tissue,  and  the  interior  of  more  compact  connective 
tissue  with  numerous  smooth  muscle  cells.  From  this  internal 
capsular  layer  septa,  or  trabeculae,  of  the  same  connective  and 
muscular  character  as  the  capsule,  run  out,  and  pass  to  the  hilum, 
where  they  divide  the  cortical  part  of  the  gland  into  various  com- 
partments known  as  alveoli.  On  joining  the  internal  or  medullary 
part  of  the  gland  the  trabecular  tissue  divides  into  finer 
strands  interconnecting  in  every  direction,  and  forming  an  open 


XIV 


THE  LYMPH 


531 


network  which  divides  the  medulla  into  a  number  of  spaces,  much 
smaller  than  the  alveoli,  that  communicate  freely  among  themselves 
to  form  a  labyrinth.  The  capsule  and  cortical  trabeculae  and  the 
network  of  medullary  septa  make  up  the  skeleton  or  supporting 
tissue  of  the  lymphatic  gland  (see  Fig.  249). 

Each  alveolus  of  the  cortex  is  occupied  by  adenoid  tissue  rich 
in  leucocytes,  in  structure  very  similar  to  a  solitary  follicle,  and 
therefore  known  as  an  alveolar  follicle.  This  is  separated  from 
the  walls  of  the  alveoli  (represented  by  the  capsule  and  trabeculae) 
by  a  lymph  sinus,  which 
merely  differs  from  that 
surrounding  a  solitary  fol- 
licle by  the  fact  that  its 
lumen  is  traversed  by  a 
larger  amount  of  reticu- 
lated tissue  (Fig.  250).  The 
medullary  spaces,  too,  are 
occupied  by  follicular  sub- 
stance in  the  form  of  rami- 
fied and  anastomosing  cords 
known  -as  the  medullary 
cords.  These  also  are  sur- 
rounded by  lymph  sinuses 
throughout  their  course. 
As  the  adenoid  tissue  of  the 
cortical  follicles  continues 
in  the  medulla  as  the  med- 
ullary cords,  so  the  circuin-  Fl( 
follicular  lymph  sinuses 
continue  in  the  spaces 
which  surround  the  medul- 
lary cords.  In  the  hiluni 
of  the  gland  the  whole  of 
the  lymph  sinuses  collect 
into  a  terminal  sinus,  which 

communicates  with  the  efferent  lymphatics.  The  afferent  lymph- 
atics, after  forming  a  plexus  between  the  two  layers  of  the  capsule, 
communicate  with  the  perifollicular  lymph  sinuses.  Like  the 
lymph  sinuses  of  the  solitary  follicle,  those  of  the  glands  are 
invested  with  epithelioid  platelets  as  shown  by  the  silver  nitrate 
reaction. 

The  small  arteries  which  penetrate  into  the  hiluni  of  the  gland 
ramify  along  the  trabecular  skeleton,  here  and  there  giving  off 
branches  that  traverse  the  sinuses  and  plunge  into  the  adenoid 
tissue,  where  they  are  resolved  into  a  capillary  network  that 
extends  to  the  medullary  cords  and  the  follicles  contained  in  the 
alveoli.  The  small  veins  that  arise  from  the  capillary  rete  also 


J.  250. — Cortical  section  of  lymphatic  gland  of  man. 
through  capsule,  cortical  sinus,  and  peripheral  portion 
of  a  follicle.  Many  of  the  lymphocytes  have  been 
removed  by  the  shaking.  (Klein.)  c,  Capsule  com- 
posed of  external  fibrous  stratum,  and  internal  layer 
of  flat,  nucleated  corpuscles  of  connective  tissue  ; 
x,  circumfollicular  lymph  sinus,  containing  largo 
meshed  reticulum  of  ramilied  connective-tissue  cells  ; 
a,  adenoid  tissue  of  a  follicle,  composed  of  network 
with  finer  and  more  compact  meshes.  Magnification, 
350  diameters. 


532  PHYSIOLOGY  CHAP, 

cross  the  sinuses  and  enter  the  trabeculae,  leaving  eventually  by 
the  hilum. 

The  leucocytes  which  fill  the  meshes  of  the  adenoid  tissue,, 
both  of  the  follicles  and  of  the  medullary  cords,  differ  in  no  way 
from  those  of  the  solitary  follicles  of  the  intestine.  The  follicles 
of  the  alveolar  glands  also  show  a  germinative  centre,  where  many 
leucocytes  are  seen  in  process  of  mitotic  division  (Fig.  251). 
Mitosis  can  also  be  seen  in  the  medullary  cords,  though  less 
freely. 

The  preceding  description  of  the  functions  of  the  solitary  and 


FH;.  251. — Alveolar  follicle  withladjacent  medullary  cord  of  a  lymphatic  gland,  in  man.  (Bohm.) 
/,  Follicle ;  cm,  medullary  cord  ;  cy,  germinal  centre,  in  which  many  leucocytes  are  seen 
undergoing  mitosis. 

agminated  follicles  applies  perfectly  to  the  lymphatic  glands  as 
well.  We  may  regard  the  former  as  simple  terminal  lympha- 
poietic  organs,  which  are  found  sparsely  disseminated  at  the  roots 
of  the  lymphatic  system ;  and  the  latter  as  complex  lympha- 
poietic  organs,  intercalated  along  the  course  of  the  lymphatic 
vessels,  and  therefore,  unlike  the  former,  provided  with  afferent 
and  efferent  vessels. 

After  the  microscopic  work  that  has  been  done  on  the  lymphatic 
glands  under  various  physiological  and  pathological  conditions; 
there  can  be  no  doubt  tha-t  the  leucocytes  that  subsequently  pass 


xiv  THE  LYMPH  533 

into  the  lymph  and  blood  are  generated  and  multiply  in  these 
organs.  The  most  convincing  experimental  evidence  is  that 
given  by  Briicke.  In  carnivorous  animals  the  lymphatic  glands 
of  the  mesentery  are  all  collected  into  a  large  semilunar  mass 
known  as  the  "pancreas  of  Asellius,"  which  lies  at  the  root  of 
the  mesentery.  If  a  little  lymph  is  collected  from  the  lymphatics 
of  a  cat's  mesentery,  fed  on  a  diet  as  free  from  fats  as  possible,  the 
fluid  is  clear  and  contains  hardly  any  corpuscles.  If  the  lymph 
of  the  efferent  lymphatic  of  the  so-called  pancreas  of  Asellius  is 
examined  at  the  same  time,  it  is  seen  to  be  opalescent,  and 
contains  a  great  number  of  leucocytes.  Further,  we  have  un- 
mistakable pathological  evidence  of  the  formation  of  leucocytes 
in  the  lymphatic  glands,  since  hyperplasia  of  the  lymphatic  glands 
is  associated  with  leucaemia,  that  is,  an  extraordinary  increase  of 
the  leucocytes  in  the  blood. 

The  mechanism  of  the  escape  of  leucocytes  from  the  adenoid 
tissues  where  they  are  generated  and  develop,  is  rather  more 
complicated  in  the  lymphatic  gland  than  it  is  in  the  solitary 
follicle.  It  is  certain  that  the  smooth  muscle  fibres  of  the 
capsule  and  trabeculae  have  here  an  important  function,  whether 
in  promoting  the  lymph  stream  through  the  glandular  sinuses, 
or  in  driving  the  leucocytes  out  of  the  adenoid  rete  and  propelling 
them  into  the  efferent  lymphatics.  For  when  these  muscular 
elements  contract  (as  can  be  experimentally  brought  about  by 
electrical  excitation  of  the  ganglion),  tire  capsule  and  the  trabeculae 
exert  pressure  directly  on  the  circumfollicular  sinuses  and  indirectly 
upon  the  whole  parenchyma  of  the  gland,  so  that  all  the  lymphatics 
are  emptied  like  a  squeezed-out  sponge  through  the  efferent 
lymphatics.  When,  on  the  contrary,  the  muscle  cells  relax,  the 
lymph  sinuses  swell  up  again,  and  are  filled  with  lymph  (Briicke). 
In  addition  to  this  lymph apoie tic  function,  we  may  reasonably 
hold  that  adenoid  tissues  in  general  are  the  seat  of  an  exchange 
of  materials  between  the  blood  and  the  lymph.  We  are  unable  to 
gauge  the  physiological  importance  of  this  exchange,  which  may 
be  enormous,  since  it  is  impossible  to  examine  the  phenomena 
of  absolute  deficiency  of  the  lymphatic  glands,  which  are  able  to 
act  vicariously  and  supplement  each  other.  It  is  further  probable 
that  many  of  the  katabolic  products  poured  out  by  the  tissues 
into  the  lymph  stream,  which  if  directly  reabsorbed  into  the 
blood  would  exercise  a  toxic  action,  are  rendered  innocuous  and 
even  beneficial  to  the  organism  by  the  specific  activity  of  the 
numerous  lymphatic  glands  through  which  they  pass  before 
rejoining  the  blood.  To  give  an  ..experimental  basis  to  this 
hypothesis,  Asher  and  Barbera  studied  on  the  dog  the  effect  on 
arterial  pressure  and  pulse  frequency,  of  injecting  into  the  central 
end  of  the  carotid  either  defibrinated  lymph  from  the  head  or 
neck  (obtained  by  continuous  centripetal  massage  of  those  parts, 

VOL.  i  2  M  a 


534  PHYSIOLOGY  CHAP 

so  that  it  remained  as  short  a  time  as  possible  in  the  lymphatic 
glands),  or  defibrinated  arterial,  or  lastly  venous  blood  from  the 
same  animal.  They  showed  that  it  was  only  after  injection  of  the 
lymph  that  decided  modifications  appeared  in  the  curves  01 
arterial  pressure  arid  pulse  frequency.  The  lymph  obtained  by 
continuous  massage  thus  contains  specific  substances  that  do  not 
exist  in  the  arterial  and  venous  blood  of  the  same  animal.  It 
is  therefore  probable  that  these  are  destroyed  and  modified  in  the 
adenoid  tissue  of  the  lymphatic  glands  (in  consequence,  as  it  seems 
to  us,  of  the  metabolism  of  the  leucocytes  accumulated  there  in 
large  quantities).  Gabritschewski  also  put  forward  the  suggestion 
that  the  leucocytes  absorb  certain  substances  noxious  to  the  body 
by  transforming  them  into  innocuous  substances,  a  phenomenon  to 
which  he  gives  the  name  of  pinocytosis. 

We  must  also  assign  a  protective  function,  in  the  mechanical 
sense,  to  the  lymphatic  glands,  owing  to  their  labyrinthine 
structure,  by  which  they  function  as  filters  to  arrest,  or  at  any 
r.ite  retard,  the  entrance  into  the  blood  of  many  pathogenic 
microbes.  This  is  proved  by  the  fact  that  in  miners,  and  also  in 
tobacco  smokers,  the  reticulated  tissue  of  the  bronchial  glands  is 
impregnated  with  pigment  due  to  the  particles  of  carbon  intro- 
duced into  the  bronchi  with  the  inspired  air. 

VIII.  Among  the  lymphoid  tissues  Bone  Marrow  has  acquired 
a  capital  importance,  ever  since  in  1865  Bizzozero  in  Italy  and 
Neumann  in  Germany  discovered  its  haeniapoietic  functions.  Three 
different  varieties  of  marrow  can  be  distinguished :  red  marrow, 
yellow  marrow,  and  gelatinous  marrow.  The  red  marrow  is  found 
in  the  spongy  strata  of  the  fiat  bones  and  proximal  epiphyses 
of  the  long  bones  of  the  extremities  (Neumann).  Yellow  marrow 
is  found  in  the  adult  in  the  distal  epiphyses  of  the  long  bones 
of  the  limbs,  and  is  the  result  of  infiltration  and  fatty  degeneration 
of  the  red  marrow,  which  gradually  increases  with  growth  and  old 
age.  In  consequence  of  fasting,  and  in  various  morbid  states  with 
general  emaciation,  the  yellow  is  transformed  into  gelatinous 
marrow,  but  does  not  lose  its  capacity  for  reconversion  into  yellow, 
taking  up  fresh  supplies  of  fat. 

Special  interest  attaches  to  the  red  marrow,  which  presents  a 
spongy  mass,  supported  by  reticular  adenoid  tissue  (which,  as 
already  stated,  consists  of  fixed  and  ramified  connective-tissue 
cells  and  a  rich  plexus  of  branching  blood-vessels).  The  nutrient 
arteries  that  enter  the  bones  divide  at  once  into  a  number  of 
branches,  which  resolve  themselves  into  a  capillary  network ;  this 
passes  into  a  system  of  venous  lacunae  partly  or  wholly  wanting 
in  organised  walls,  in  which  the  blood  moves  very  slowly;  out 
of  this  lacunar  or  cavernous  rete  arise  the  small  veins  by  which 
the  blood  flows  out.  It  is  notable  that  the  veins  that  occur 
within  the  medullary  tissue  are  wholly  deprived  of  valves,  while 


XIV 


THE  LYMPH 


535 


those  that  issue  from  the  bone  are  furnished  with  an  extraordinary 
number  of  them. 

The  cells  contained  in  the  lacunar  system  of  the  marrow  are 
quite  characteristic  of  this  tissue.  Among  them  four  principal 
kinds  can  be  distinguished :  leucocytes,  megacaryocyfces  (giant 
cells),  erythroblasts,  erythrocytes. 

The  leucocytes  of  bone  marrow  comprise  many  varieties,  which 


FIG.  252. —  Leucocytes  from  dog's  bone  marrow,  dry  preparation,  a,  //,  Young  leucocytesior 
lymphocytes,  with  giant  nuclei  and  little  cytoplasm  ;  c,  d,  medullary  cells  or  adult  leucocytes 
with  reniform  and  polymorphous  nuclei  ;  e,  leucocytes  undergoing  mitotic  division. 

probably  represent  different  states  of  development  of  a  single 
cellular  type,  since  there  are  always  numerous  transitional  forms 
from  the  one  to  the  other  variety.  The  differences  lie  in  the 
dimensions,  form  of  nucleus, 
and  character  of  cytoplasm. 
The  youngest  (lymphocytes) 
are  the  smallest,  owing  par- 
ticularly to  the  paucity  of  pro- 
toplasm around  the  nucleus ; 
the  disc -shaped  nucleus  is 
rich  in  chromatin.  The  more 
adult  (medullary  cells)  are 
larger,  with  a  reniform 
polymorphous,  sometimes 
multiple  nucleus,  poor  in 
chromatin.  These  are  not 
found  in  normal  circulating 
blood,  only  in  states  of  leu- 
caemia (Fig.  252). 

Howell's  megacaryocytes 
were  discovered  in  1869  by 
Bizzozero,  who  called  them  giant  cells  with  a 
nucleus.  They  have  an  average  diameter  of  25-45  //.  Their 
nucleus  is  very  variable  in  form,  often  horseshoe-shaped.  Heiden- 
hain  distinguishes  several  types  or  varieties  according  to  the  different 
degree  of  differentiation  of  the  cytoplasm,  which  is  sometimes 
arranged  in  three  concentric  zones  (Fig.  253).  Bizzozero  had 
already  suggested  that  the  giant  cells  were  derived  from  the 
leucocytes  of  bone  marrow,  since  there  is  a  whole  series  of  forms 


FIG.  2;13. — Megacaryocyte  of  bone  marrow,  in  which 
a  large  horseshoe  nucleus  can  be  distinguished 
from  the  cytoplasm,  divided  into  three  concentric 
zones.  (Heidenhain.) 


budding  central 


536 


PHYSIOLOGY 


CHAP. 


intermediate  between  the  two.  The  leucocytic  origin  of  the  giant 
cells  is  nowadays  admitted  by  every  one,  although  the  process  by 
which  the  one  form  of  cell  passes  into  the  other  is  still  unknown. 

The  erythrocytes,  or  nucleated  red  corpuscles,  were  described 
in  1868  by  Bizzozero  and  Neumann,  who  recognised  that  they 


Fin.  254. — Erythroblasts  and  erythrocytes  from  bone  marrow  of  dog,  dry  preparation.  «,  l>,  c, 
Erythroblasts  with  more  or  less  developed  and  excentric  nucleus  ;  d,  erythroblasts  in  mitotic 
division  ;  e,  f,  erythrocytes  apparently  destitute  of  nucleus. 

contained  haemoglobin.  Among  them  may  be  distinguished 
young  forms,  adults,  and  those  undergoing  mitotic  division.  They 
can  easily  be  differentiated  from  the  lymphocytes  of  the  same  size, 
not  only  by  the  haemoglobin  which  they  contain,  but  also  by  the 


FIG.  255. — Preparation  of  human  bone  marrow,  showing  the  various  migratory  cells,  implanted  in 
the  lacunae  of  an  adenoid  tissue,  leaving  large  irregular  spaces  here  and  there,  which  are 
occupied  by  adipose  tissue.  (B<">hm  and  v.  Davidott'.) 

different  reaction  of  their  cytoplasm  to  certain  stains.  Erythro- 
blasts never  in  their  different  stages  of  development  present  any 
cytoplasmic  granulation,  such  as  stains  with  indulin  (Trambusti). 
In  their  constitution  as  in  their  size,  the  erythroblasts  exactly 
resemble  the  apparently  non-nucleated  erythrocytes  of  the  blood, 
which  are  found  mingled  with  the  nucleated  cells  of  bone  marrow. 


XIV 


THE  LYMPH 


537 


Fig.  255  gives  an  idea  of  the  mode  in  which  these  multiple 
elements  are  connected  and  intermingled  in  the  areolar  tissue  of 
human  bone  marrow. 

From  what  has  been  said,  the  great  functional  importance 
of  bone  marrow  will  readily  be  admitted.  The  red  marrow,  like 
all  other  lymphoid  tissues,  certainly  contributes  to  lymphapoiesis, 
owing  to  its  content  of  leucocytes  at  various  stages  of  development. 
Since  the  different  varieties  of  leucocytes  differ  in  chemical 
constitution  —  inasmuch  as  they  show  granulations  that  stain 
differently  with  special  pigments — it  is  not  improbable  (as  sug- 
gested by  Trambusti)  that  their  specific  metabolism  may  serve  for 
special  functions,  of  which,  however,  we  are  at  present  entirely 
ignorant. 

It  is  more  interesting  to  consider  the  functions  of  the  mega- 


FKJ.  250. — Megaearyocyte  of  bone  marrow,  with  resting  nucleus  and  linely  granular  cytoplasm, 
differentiated  into  three  layers,  and  containing  five  leucocytes  in  process  of  digestion. 
(Trambusti.) 

caryocytes,  on  which  much  work  has  been  done.  The  cytoplasm  of 
some  of  these  (particularly  in  the  first  stages  of  acute  infections 
experimentally  produced  in  animals)  often  contains  corpuscles, 
which  in  their  characteristics  in  no  way  differ  from  common 
leucocytes  (Fig.  256).  They  were  at  first  regarded  as  leucocytes 
in  process  of  formation  by  endogenous  mitosis,  or  gemmation  of 
the  nucleus  of  giant  cells.  Later  researches  have  shown,  however, 
that  they  are  worn-out  leucocytes  in  process  of  degeneration, 
which  are  actively  absorbed  by  the  giant  cells,  and  are  destined  to 
be  digested  by  them.  It  is  possible  under  the  microscope  to 
follow  the  different  phases  of  digestive  necrosis  of  the  ingested 
leucocytes,  by  means  of  double  staining  with  safraniu  and  indulin 
(Trambusti).  These  observations  exclude  the  suggestion  of 
Heidenhain,  that  in  cases  in  which  leucocytes  are  included  in 
giant  cells  the  former  are  the  active  invaders,  and  the  latter  the 


538  PHYSIOLOGY  CHAP. 

passive  victims  doomed  to  destruction.  Other  observations, 
moreover,  show  that  when  the  giant  cells  exhibit  signs  of  necrosis, 
they  never  contain  leucocytes,  as  would  be  the  case  if  Heidenhain's 
interpretation  were  true.  It  is  evident,  therefore,  that  the 
inegacaryocytes  fulfil  a  phagocytic  function  within  the  body,, 
which  probably  serves  to  free  the  lymphapoietic  organs  from  the 
leucocytes  that  are  dead  or  in  process  of  dissolution  (van  der 
Stricht). 

P.  Foa  (1899)  has  recently  investigated  the  experimental 
conditions  under  which  it  is  possible  to  obtain  the  phenomenon 
of  phagocytosis  upon  a  large  scale  with  these  uiegacaryocytes.  He 
found  it  appeared  vigorously  in  inanition,  extensive  burning  of 
the  skin,  and  with  intravenous  injections  of  lecithin,  milk,  and 
bacterial  proteins,  especially  in  gravid  or  very  young  rabbits 
of  VOD-SOO  grams,  in  weight.  Under  all  these  conditions  the 
megacaryocytes  were  seen  to  contain  numerous  polymorphous 
leucocytes  within  their  protoplasm,  some  of  which  had  already 
undergone  protoplasmic  dissolution  and  nuclear  fragmentation,  on 
the  way  to  their  complete  disappearance.  At  the  same  time,  the 
protoplasm  of  the  inegacjiryocytes  was  seen  to  undergo  alteration 
and  disruption,  and  their  nucleus  shrank,  and  passed  free  into  the 
circulatory  torrent,  where  it  blocked  the  capillaries  of  the  lungs 
and  was  finally  disintegrated.  These  two  phenomena :  destruction 
of  leucocytes  by  the  megacaryocytes,  and  embolism  of  pulmonary 
capillaries  by  the  liberated  nuclei  of  the  giant  cells,  are  always- 
combined,  and  may  be  noted  in  a  lesser  degree  under  normal 
conditions  as  well,  particularly  during  pregnancy.  In  pathological 
states  the  phenomenon  is  exaggerated,  and  indicates  destruction  of 
leucocytes  that  are  no  longer  capable  of  functioning.. 

Other  notable  facts  show  that  the  megacaryocytes  exert  an 
important  secretory  function  in  regard  to  the  regeneration  of  the 
blood.  In  fact,  after  repeated  bleeding  of  the  rabbit,  their  number 
conspicuously  increases  (van  der  Stricht,  Bambeke,  Heidenhain). 
The  external  zone  of  their  cytoplasm  (which  stains  less  readily) 
exhibits  bud-like  protuberances,  which  increase  in  volume,  and 
become  clearer  in  consequence  of  the  increasing  amount  of  fluid 
imbibed  by  the  delicate  reticulum  (Fig.  2'53).  At  a  later  stage 
the  said  buds  fuse  one  into  the  other,  and  form  large  clear  vesicles, 
in  which  it  is  no  longer  possible  to  distinguish  the  protoplasmic 
network.  When  the  intracellular  tension  of  the  secretory 
product  has  reached  its  maximum,  the  fluid  pours  out,  and  the 
distended  protoplasmic  reticulum  contracts  again  to  form  a  new 
external  stratum  of  cytoplasm.  It  should  be  noted  that  the  bone 
marrow  of  rabbits  which  have  been  freely  bled  seldom  exhibits 
leucocytes  ingested  by  giant  cells,  showing  that  under  these 
conditions  the  secretory  function  of  the  latter  predominates. 

We  are  ignorant  of  the  precise  physiological  destination  of  the 


xiv  THE  LYMPH  539 

products  elaborated  in  the  giant  cells.  But  from  the  very  im- 
portant fact  discovered  by  van  der  Stricht  to  the  effect  that  in  a 
case  of  progressive  pernicious  anaemia  there  was  complete  absence 
of  giant  cells  in  the  bone  marrow,  it  may  be  assumed  that  they 
are  useful  to  the  production  of  erythrocytes. 

The  simultaneous  presence  in  bone  marrow  of  erythroblasts 
(nucleated  embryonic  red  corpuscles)  and  erythrocytes  (adult  red 
corpuscles  with  no  visible  nuclei)  shows  beyond  doubt  that  it 
is  the  seat  of  an  active  formation  of  the  latter  which  are 
found  in  the  blood  in  large  numbers.  After  repeated  bleeding  the 
haematopoietic  function  of  the  bone  marrow  is  conspicuously 
increased.  The  number  of  haematoblasts  undergoing  mitotic 
division  increases ;  even  that  part  of  the  marrow  of  the  long 
bones  which  is  normally  inactive  assumes  a  haematopoietic  function 
(Orth,  Litten,  Foa  and  Pellacani,  Bizzozero  and  Salvioli).  Under 
these  conditions  a  large  number  of  nucleated  red  corpuscles  enter 
the  circulatory  torrent  (Erb). 

Alterations  in  bone  marrow  can  also  be  observed  in  many 
diseases  in  which  there  is  marked  alteration  of  the  corpuscles 
(leucaemia,  pernicious  anaemia,  typhoid,  smallpox). 

According  to  Danilewski  and  Selenski  the  subcutaneous  or 
intraperitoneal  injection  of  watery  extracts  of  bone  and  splenic 
marrow  produces  a  considerable  increase  in  the  number  of 
erythrocytes  (up  to  50  per  cent)  and  the  haemaglobin  content 
(up  to  40  per  cent)  of  the  blood  of  rabbits  and  dogs.  This  effect 
was  confirmed  by  Fowler  in  regard  to  extract  of  bone  marrow. 

It  was  formerly  admitted  (Bizzozero),  and  is  still  retained  by 
some  authors  (Paladino),  that  erythrocytes  arise  from  direct 
transformation  of  leucocytes.  This  theory,  for  which  there  is 
no  experimental  evidence,  is  now  being  given  up.  The  only 
well-established  fact  is  that  the  erythrocytes  increase  by  mitotic 
division. 

On  the  other  hand  it  is  certain  that  adul-t  erythrocytes  are 
derived  from  embryonic  haematoblasts.  The  blood  of  the  human 
foetus  at  the  fourth  month  contains  only  nucleated  red  corpuscles  ; 
at  the  end  of  the  ninth  month  these  have  become  very  rare. 
After  that  they  are  completely  replaced  by  erythrocytes  with  no 
perceptible  nucleus.  How  does  the  disappearance  of  the  embryonic 
nucleus  of  the  mammalian  erythrocyte  come  about  ?  Eindneisch 
asserts  that  there  is  active  extrusion  of  the  nucleus ;  the  haemato- 
blast  is  deformed  into  the  shape  of  a  bell  or  watch-glass,  the 
vertex  of  which,  containing  the  nucleus,  is  finally  disrupted.  The 
bi-concavity  of  the  erythrocytes  is  a  vestige  of  this  enucleation, 
which  may  be  regarded  as  a  kind  of  autocastration.  The  majority 
of  observers  hold  more  simply  that  the  embryonic  nucleus 
atrophies  gradually,  and  ends  by  disappearing.  If,  however,  this 
view  were  well  founded  we  ought  to  find  a  number  of  transitional 


540  PHYSIOLOGY  CHAP. 

forms  intermediate  between  the  erythroblast  and  the  eventual 
erythrocyte,  whereas,  on  the  contrary,  every  one  admits  that  the 
transitory  forms  are  rarely  met  with.  The  question  must,  there- 
fore, be  regarded  as  unsolved. 

Petrone  (1898-99)  thought  he  had  demonstrated  that,  while 
apparently  deprived  of  nuclei,  the  erythrocytes,  when  subjected  to 
the  action  of  special  reagents,  contain  a  body  which  has  all  the 
cytological  and  chemical  characters  of  the  nucleus.  In  order  to 
see  this  it  is  only  necessary  to  make  an  extract  of  living  blood 
with  a  1  in  4000  solution  of  osmic  acid.  In  successful  preparations 
the  erythrocytes  are  seen  under  the  microscope  to  be  in  good 
preservation,  perfectly  globular  (no  longer  bi-concave),  with  a 
homogeneous  content.  At  the  centre,  or  more  or  less  at  one  side, 
they  exhibit  a  body  with  wavy  or  dentate  outline,  in  which  a  fine 
filamentous-granular  structure  may  be  detected.  This  alone  stains 

electively    with     nuclear 

/^^.^  ^flhfev    s^a^ns'  while  the  rest  of  the 

\         &  x\          /^     H    erythrocyte     stains     with 

/        r  ?;          Vs       '3y    protoplasmatic  dyes  (Fig. 

$s  x-_>^    257).  According  to  Petrone 

the   supposed   nucleus  of 
the    circulating    erythro- 

/^  /^ .  ML      cytes  is  almost  always  in 

I^B^^H     a  s^e  °f  complete  rest, 
\|  although  he  thinks  it  pre- 

mature  to  say  that  it  is 

FIG.    257.- Erythrocytes   of  healthy   man,   -showing   the  entirely     lacking     in  gCI- 

more  or  less  central    or  excentric  corpuscles  which  minative       activitv  He 

Petrone  holds  to  be  permanent  nuclei.     From  blood  .  J  ' 

immersed  in  1:4000  osmic  acid,  subsequently  treated  thinKS     it      probable  that 

with  baths  of  picric  acid,  and  then  stained  with  formic  ji   *r       J~  J~  j.u 

haematoxylin  and  aurantia.  thlS      depends      Upon  the 

comparatively    short    life 

of  the  erythrocyte,  and  the  predominance  of  a  special  iron-carrying 
haemoglobinogenic  function  which  he  attributes  to  it. 

The  work  of  Negri  (1900),  however,  invalidates  Petrone's 
conclusion  that  the  part  of  the  protoplasm  which  is  shown  up  by 
his  method  of  staining  can  really  be  interpreted  as  the  nucleus  of 
the  erythrocytes.  Negri  found  that  this  characteristic  body  can 
always  be  demonstrated,  on  using  Petrone's  method,  in  the  true- 
nucleated  erythrocytes  as  well,  independent  of  the  nucleus  proper, 
both  in  the  blood  of  the  mammalian  embryos  and  in  the  blood  of 
such  adult  animals  as  normally  contain  nucleated  corpuscles  (birds 
and  amphibia). 

IX.  Among  the  lymphoid  organs  we  must  also  include  the 
Thymus,  which  consists  of  a  collection  of  closed  follicles,  separated 
by  septa  or  trabeculae  of  connective  tissue.  The  section  of  a  lobe 
of  the  thymus  shows  under  a  small  magnification  a  cortical  and  a 
medullary  substance,  which  recalls  the  structure  of  the  lymphatic 


xiv  THE  LYMPH  541 

glands  (Fig.  258).  The  reticulated  adenoid  tissue  and  a  rich 
network  of  blood  capillaries  support  it,  with  finer  meshes  in  the 
cortical  part  and  wider  meshes  in  the  medulla.  The  cellular 
elements  of  the  reticulum  are  collected  more  abundantly  in  the 
former  than  in  the  latter.  The  arrangement  and  relations  of  the 
lymphatic  vessels  in  the  thymus  are  still  imperfectly  determined. 
The  thymus  begins  to  develop  in  the  earliest  periods  of 
embryonic  life.  In  man  the  development  is  rapid  between  the 
third  and  ninth  months.  It  is,  however,  a  fallacy  to  hold  that  the 
thymus  is  exclusively  a  foetal  organ,  because  it  continues,  though 
slowly,  to  grow  after  birth,  up  to  the  second  year  of  life ;  it 
remains  stationary  till  the  tenth  year,  after  which  it  gradually 
atrophies  and  undergoes  fatty  degeneration.  The  process  of 
involution  is  not  unusually  much  retarded  :  it  is  found,  for  example, 


Pio.  258.— Section  of  lobule  of  child's  thymus.  (Buhm  and  v.  Davidott.)  The  hiluin  and  critical 
substance  are  seen  in  distinct  follicles,  separated  by  delicate  trabeculae,  while  the  medullary 
substance  is  formed  by  an  adenoid  tissue  with  larger  meshes. 

at  the  age  of  twenty-five ;  even  at  an  advanced  age  the  thymus 
has  been  found  well  developed. 

From  the  fact  that  in  reptiles  and  amphibia  which  have  no 
lymphatic  glands  the  thymus  is  a  persistent  organ,  functioning 
during  the  whole  of  life,  we  may  conjecture  that  its  functions  are 
very  similar  to  those  of  the  lymph  glands. 

That  we  must  ascribe  to  it  a  lymph apoietic  function  is  shown 
by  the  fact  that  the  majority  of  the  cells  contained  in  its  follicles 
are  represented  by  lymphocytes  of  varying  magnitude,  some  of 
which  may  be  seen  undergoing  mitotic  division.  Whether  it  also 
has  a  haemopoietic  function  is  less  certain,  although  some  have 
distinguished  among  the  thymus  cells  nucleated  red  corpuscles, 
i.e.  erythroblasts  proper,  such  as  are  observed  in  bone  marrow. 

Eecent  physiological  work  on  the  effect  of  total  or  partial 
extirpation  of  the  thymus,  performed  on  puppies  and  chickens  at 
different  stages  of  development,  and  particularly  on  frogs,  has 


542  PHYSIOLOGY  CHAP. 

brought  to  light  some  very  interesting  phenomena,  which  indicate, 
however  indefinitely  and  incompletely,  the  functional  importance 
of  this  organ. 

Kestelli  (1845)  was  the  first  who  attempted  extirpation  of  the 
thymus  on  lambs,  dogs,  and  calves,  without,  however,  obtaining 
any  practical  results.  Friedleben  (1858)  resumed  the  experiments 
with  better  success.  He  succeeded  in  keeping  alive  several  dogs 
on  which  lie  had  operated  by  excising  the  thymus  alone,  or  the 
thymus  and  spleen  together.  He  did  not,  however,  pay  much 
attention  to  the  age  of  the  animals  on  which  he  was  experimenting, 
nor  did  he  undertake  comparative  experiments  under  perfectly 
comparable  conditions.  In  the  animals  deprived  of  their  thymus 
he  noted  increase  of  water  in  the  blood  (hydraemia),  increase  of 
leucocytes  (leucocythaeinia),  and  diminution  of  erythrocytes  (oligo- 
cythaemia) ;  conspicuous  reduction  in  the  carbonic  acid  given  off 
in  the  time  unit ;  general  trophic  disturbances,  particularly  in  the 
bony,  and  also  in  other  tissues.  He  concluded  that  the  thymus  is 
not  an  organ  indispensable  to  life,  although  it  if,  highly  important 
shortly  after  birth,  since  during  the  development  of  .the  body  it 
promotes  nutrition,  formation  of  the  blood,  and  also,  therefore,  of 
the  tissues.  Nothing  was  added  to  these  results  in  a  short  paper 
published  by  Langerhans  and  Savaliew  (1893). 

At  the  International  Medical  Congress  in  Eonie  (1894)  Tarulli 
and  Lo  Monaco  communicated  the  first  results  of  their  experiments 
as  performed  in  our  laboratory,  which  were  subsequently  completed 
and  published  in  a  larger  memoir. 

By  means  of  the  Thoma-Zeiss  method,  they  confirmed  the  fact 
already  stated  by  Friedleben,  to  the  effect  that  dogs  deprived  of 
their  thymus  exhibited  a  more  or  less  pronounced  state  of  anaemia, 
consisting  in  a  diminution  of  erythrocytes  and  increase  of  leuco- 
cytes. They  added,  however,  that  this  was  only  a  temporary 
effect,  and  that  two  or  three  months  after  the  operation  the 
number  of  blood-corpuscles  became  almost  equal  to  that  of  the 
normal  dogs  born  in  the  same  litter. 

Puppies  deprived  of  their  thymus  are  stunted  in  growth,  weigh 
less,  and  have  more  flaccid  muscles  than  the  control  animals.  The 
difference  is  especially  conspicuous  a  month  or  a  month  and  a  half 
after  the  operation  ;  later  on  it  dies  out  gradually,  and  cannot  be 
detected  after  about  three  months.  The  hair  differs  both  in  length 
and  pigmentation  in  puppies  with  and  without  a  thymus.  Gener- 
ally speaking  the  coat  of  the  latter  is  rougher,  without  the  normal 
gloss  and  resistance,  and  yields  to  the  slightest  pressure.  Sometimes 
the  bones  of  the  limbs  are  longer,  thinner,  and  more  bowed  in 
puppies  with  no  thymus ;  sometimes  there  is  an  exaggerated 
development  of  head  at  the  expense  of  the  rest  of  the  body. 

Puppies  with  no  thymus  further  show  reduced  resistance  and 
capacity  for  muscular  work  ;  they  seldom  leave  their  bed,  and  are 


xiv  THE  LYMPH  543 

tired  after  a  lew  steps;  they  can  hardly  drag  a  weight  much 
lighter  than  that  drawn  easily  by  normal  puppies.  The  difference 
is  very  marked  even  two  months  after  the  operation  ;  it  then 
diminishes,  and  finally  disappears.  In  the  first  two  months  after 
the  operation  these  puppies  easily  fall  ill  and  die  without  any 
particular  cause.  Nothing  abnormal  can  be  detected  at  the  post- 
mortem, except  that  the  gastro-intestinal  mucosa  is  congested. 

The  effects  of  extirpating  the  thymus  in  chicks  4  to  5  days  old 
are  more  apparent.  Immediately  after  the  operation  they  exhibit 
only  the  effects  of  operative  traumatism,  which  soon  passes  off,  so 
that  nothing  abnormal  is  seen  the  next  day.  Three  to  four  days 
after  the  operation,  however,  motor  disturbances  appear,  and  go  on 
increasing :  weakness  of  limbs,  uncertain  gait,  slight  tremors  of  all 
the  muscles,  finally  torpor,  followed  shortly  after  by  death.  In  18 
operated  chicks,  15  died  with  these  symptoms  7  to  8  days  after 
the  operation ;  2,  in  which  the  disturbances  were  less  pronounced, 
recovered  after  10  to  12  days:  one  only  succumbed  during  the 
operation. 

Of  6  chicks,  deprived  of  the  thymus  on  one  side  only,  one 
alone  (operated  on  2  days  after  birth)  perished,  the  symptoms 
resembling  those  of  chicks  in  which  both  sides  were  operated  on  : 
the  others  survived,  merely  exhibiting  a  slight  weakness  in  the 
first  days  after  the  operation. 

In  chicks  of  10  to  25  days  the  excision  of  the  thymus,  either  on 
one  side  or  on  both,  produced  no  perceptible  effect. 

In  the  interval  between  the  first  and  second  publications  of 
Tarulli  and  Lo  Monaco,  two  French  experimenters,  Abelous  and 
Billard  (1896),  published  their  work  on  the  effect  of  thymus 
extirpation  in  the  frog,  which  (as  might  be  anticipated)  is  more 
marked  than  in  the  case  of  birds,  the  thymus  in  amphibia  being  a 
permanent  organ,  functioning  throughout  life. 

One  to  two  days  after  the  bilateral  excision  of  the  thymus,  the 
frog  exhibits  serious  motor  disturbances,  as  shown  in  progressive 
muscular  debility  and  incapacity  for  work,  which  increases  till  it 
amounts  to  paresis,  paralysis,  and  the  death  of  the  animal.  It  is 
remarkable  that  while  neuro-muscular  activity  becomes  exhausted, 
sensibility  remains  intact,  and  even  increases  at  first. 

Some  hours  after  the  operation  the  copper-green  colour  of  the 
frog  (Rana  esculenta)  changes  to  a  yellowish  hue,  and  the  area  of 
black  spots  is  contracted ;  only  the  head  and  limbs  escape  this 
discoloration.  On  the  following  day  this  phenomenon  is  less 
pronounced  ;  with  the  onset  of  the  muscular  weakness  it  reappears, 
and  increases  steadily  till  death.  Along  with  the  discoloration 
dystrophic  effects  begin  to  appear  On  the  skin  in  the  form  of 
ulcers,  zones  of  necrotic  destruction,  and  subaponeurotic  ecchymoses. 
These  changes  become  more  serious  the  longer  the  animal  survives. 
The  ulcerated  surfaces  are  highly  hyperaemic,  and  bleed  at  the 


544  PHYSIOLOGY  CHAI>. 

least    touch.      These    animals    may    be    said    to    have    become 
haemophilia. 

Most  frogs  at  the  moment  of  death  exhibit  dropsy.  Directly 
the  abdomen  is  opened  or  the  muscles  cut  through,  a  colourless  or 
bloody  transudate  escapes. 

The  blood  from  the  heart  is  more  watery  ;  the  erythrocytes  are 
changed  in  form  and  colour,  and  are  fewer  in  number,  while  the 
leucocytes  are  increased.  The  peritoneum,  bladder,  stomach, 
intestine,  other  abdominal  viscera,  and  the  cervical  region  of  the 
cord  are  all  more  or  less  congested. 

Undoubtedly  death  results  from  functional  defect  of  both  lobes 
of  the  thymus.  It  invariably  occurs,  but  after  an  interval  which 
varies  from  3  to  4  days.  It  ensues  equally  when  the  two  organs 
are  excised  at  different  times,  with  a  longer  or  shorter  interval 
between  the  two  operations.  After  the  extirpation  of  one  thymus 
only  nothing  abnormal  appears  save  a  lessened  resistance  to 
fatigue.  If  the  second  thymus  is  exposed  15  to  20  days  after,  it 
exhibits  a  certain  degree  of  hypertrophy.  Its  excision  is  rapidly 
followed  by  the  disturbances  aloove  described,  and  death  ensues  in 
a  short  time. 

If  the  blood  or  serum  from  the  peritoneal  cavity  of  a  frog  that 
is  dying  from  ablation  of  its  thymus  glands  is  injected  into  a 
frog  that  is  normal  or  deprived  of  one  or  both  thymuses,  more  or 
less  pronounced  disturbances  of  function  will  be  observed  in  all, 
which  may  produce  death  even  in  normal  frogs,  induce  it  almost 
inevitably  in  frogs  with  only  one  thymus,  and  greatly  accelerate 
it  in  frogs  deprived  of  both  organs.  This  fact  shows  that  the 
tissue  fluids  of  the  frog  entirely  deprived  of  thymus  contain 
energetically  toxic  substances,  and  that  the  fundamental  function 
of  the  organ  consists  in  the  destruction  of  these,  or  in  rendering 
them  innocuous. 

Transplantation  or  grafting  of  the  excised  thymus  beneath  the 
skin  of  the  same  frog  or  of  another  deprived  of  its  thymus,  does 
not  inhibit  the  phenomena  of  auto-intoxication  above  described. 
Abelous  and  Billard,  however,  observed  a  temporary  abatement  of 
the  phenomena  of  discoloration.  On  the  other  hand,  subcutaneous 
injection  of  extract  of  calves'  thymus  (calves'  thymus  20  grms.,  solu- 
tion of  boric  acid  100  grrus.)  in  1  c.c.  doses  containing  0'02  grm.  of 
thymus,  both  in  normal  frogs  and  in  those  which  have  been  partly 
or  wholly  deprived  of  the  thymus,  produce  effects  resembling 
strychnine  convulsions,  while  at  the  same  time  cutaneous  dis- 
coloration ceases,  and  the  normal  colour  of  the  skin  becomes 
more  pronounced.  Accordingly  there  is  a  true  antagonism 
between  the  phenomena  of  thymus  deficiency  and  those  produced 
by  injection  of  the  extract  of  this  organ. 

Ver  Eecke  (1899)  also  worked  on  the  frog's  thymus,  coming  to 
conclusions  which  differed  in  some  respects  from  those  of  Abelous 


xiv  THE  LYMPH  545 

and  Billard.  According  to  ver  Eecke  the  function  of  the  frog's 
thymus  is  subject  to  periodical  oscillations  similar  to  those  of 
bone  marrow.  He  found  that  the  frog's  thymus  undergoes 
functional  atrophy  in  winter,  and  an  analogous  state  can  also  be 
observed  in  summer  if  the  frog  is  made  to  fast.  The  functions  of 
the  thymus  are  thus  closely  associated  with  those  of  the  digestive 
organs.  Possibly  it  further  has  an  antitoxic  action.  Both  during 
the  winter  season  and  in  summer,  if  the  animal  is  made  to  fast,, 
the  thymus  is  not  indispensable  to  life.  Its  partial  or  total 
excision,  whether  uni-  or  bi-lateral,  under  these  conditions  has  no 
effect  other  than  to  weaken  the  resistance  of  the  animal  to  external 
intoxications. 

Basch  (1903),  after  thymus  extirpation,  noticed  alterations  in 
the  ossification  of  the  long  bones.  In  animals  without  a  thyinus 
the  formation  of  callosities  and  union  of  the  fractured  bones 
occurred  later  than  in  the  normal.  The  animals  operated  on 
eliminated  a  larger  amount  of  calcium  than  the  control  animal, 
amounting  sometimes  to  five  times  the  quantity. 

Svehla  (1896-1900),  on  injecting  a  watery  extract  of  the 
thymus  of  man  and  other  animals  (pig,  ox,  dog)  into  the  circula- 
tion, noted  in  dogs  that  there  was  acceleration  of  pulse  and 
diminution  of  blood  pressure,  an  effect  resembling  that  of  the 
injection  of  thyroid  and  suprarenal  extracts.  According  to  the 
latest  experiments,  it  appears  more  probable  that  this  action  of 
thymus  extract  is  due  not  to  a  specific  substance  in  the  thymus — 
as  is  the  case  with  the  suprarenal  capsule — but  to  the  various 
substances,  nucleoproteins  in  particular,  which  are  dissolved  in  the 
water,  and  are  found  generally,  without  exception,  in  every  organ. 
A  similar  action  has  in  fact  been  observed  after  the  injection  of 
extracts  of  many  other  organs  (Hammarsten). 

Cervesato  attempted  organotherapy  with  the  thymus,  starting 
from  the  fundamental  concept  that  this  organ  in  man  functioned 
during  infancy,  and  that  this  may  be  the  reason  why  infants  are 
less  readily  attacked  by  or  are  even  immune  from  certain  diseases. 
Stoppato  describes  the  results  obtained  by  the  administration  as  a 
food  of  raw  or  undercooked  thymus  in  doses  of  29-40  grms.  a  day, 
in  four  cases  of  infantine  atrophy,  and  in  one  case  of  infantine 
anaemia.  In  all  these  he  obtained  very  encouraging  results  after 
a  two -months'  regime  ;  there  was  marked  improvement  in  the 
general  state  of  nutrition,  with  development  of  body  weight  and 
increase  of  erythrocytes  and  haemoglobin  of  the  blood.  On  the 
other  hand,  the  results  obtained  from  children  afflicted  with  rickets 
and  abdominal  scrofula  were  insignificant,  which  points  to  the 
specific  character  of  the  therapeutic  action,  and  therefore  to  the 
normal  function  of  the  thymus  as  an  organ  affecting  general 
metabolism. 

X.  The  Spleen  is  the  largest  lymphoid  organ,  its  structure 
VOL.  i  2  N 


546  PHYSIOLOGY  .  CHAP. 

corresponding  to  that  of  the  lymphatic  glands,  thymus,  and  red 
bone  marrow — which  justifies  us  in  assuming  that  the  function  of 
all  these  organs  (apart  from  their  specific  differences)  is  closely 
allied,  so  that  they  are  to  some  extent  able  to  supplement  each 
other,  or  to  act  vicariously.  Besides  its  peritoneal  sheath  the 
spleen  has  a  capsule,  consisting  of  fibrous  elastic  and  muscular 
tissue.  A  number  of  trabeculae  dip  into  the  organ  from  the  inner 
surface  of  the  capsule,  dividing  and  subdividing,  so  that  the 
parenchyma  is  converted  into  an  elastic  and  contractile  network, 
with  large  and  small  meshes,  the  hollow  spaces  of  which  contain 
the  so-called  splenic  pulp  (Fig.  250). 


Fi<;.  ^59.— Vertical  section  through  a  fragment  of  human  spleen,  low  magnification.  (Kolliker.) 
A,  Peritoneal  and  librous  capsule ;  b,  b,  trabeculae ;  c,  c,  Malpighian  corpuscles,  one  of 
which  shows  the  transverse  section,  and  the  other  the  long  section,  of  an  artery  ;  d,  injected 
arterioles  ;  e,  splenic  pulp. 

When  the  spleen  is  cut  across  and  squeezed,  the  pulp  escapes, 
looking  like  blackish  coagulated  blood,  which  after  exposure  to  the 
air  assumes  a  lighter  reddish  hue.  On  examining  a  thin  section 
of  spleen  treated  with  dilute  solution  of  potash  under  the  micro- 
scope, the  splenic  pulp  is  seen  to  be  contained  within  the  unequal 
meshes  of  a  lymphoid  tissue  that  supports  it,  and  is  composed  of 
fringed  connective  cells,  which  ramify  and  anastomose  among 
themselves,  and  are  in  connection  with  the  trabecular  tissue 
(Fig.  260). 

The  splenic  vein  and  artery  are  remarkable  for  their  size 
relative  to  the  volume  of  the  body  which  they  irrigate.  After 
penetrating  the  hilum  to  the  interior  of  the  spleen  by  six  or  more 
branches,  they  ramify  dendritically,  still  within  the  trabeculae, 


XIV 


THE  LYMPH 


547 


which  cover  them  with  an  adventitious  lyniphoid  sheath.  In  the 
small  arteries  this  sheath  dilates  here  and  there  into  grey  nodules, 
oval  or  spherical,  of  various  sizes  (1-0'36  mm.  in  diameter),  similar 
in  structure  to  the  solitary  follicles  of  the  intestine,  and  known  as 


FIG.  '260. — Thin  section  of  splenic  pulp  neai1  the  origin  of  a  small  vein,  highly  magnified.  (E.  A. 
Schafer.)  v,  Venule  filled  with  red  and  white  blood-corpuscles ;  bl,  erythrocytes  which  till 
the  interstices  of  the  reticular  tissue  of  the  pulp  ;  p,  branching  connective-tissue  cells  which 
form  the  reticulum  containing  the  pulp. 

Malpighian  nodules  or  corpuscles,  after  their  discoverer.  These 
nodules,  for  the  most  part,  develop  laterally  to  the  small  arteries, 
from  which  they  receive  twigs  that  irrigate  the  follicular  tissue 
(Fig.  261).  Under 
the  high  power,  each 
Malpighian  corpuscle 
shows  a  complex  reti- 
cular structure,  by 
which  they  are  differ- 
entiated from  the 
hoinonymous  tissue  of 
the  splenic  pulp  (as 
shown  in  Fig.  262, 
which  represents  a 
preparation  obtained 
by  the  silver  chromate 
method). 

The  small  arterial 

ranii,  after  leaving  the  FIO.  -201.—  Small  splenic  artery  (dog),  with  many  Malpighian 
r  i  ,  -i  corpuscles  attached  to  the  peri  vascular  lymphatic  sheath ; 

trabecular  tissue  and       m^flcationofiodtebetew:  (iwiiiker.) 
penetrating  the  areolar 

labyrinthine  tissue  which  contains  the  pulp,  divide  into  small 
feathered  tufts  of  arterioles;-  they  afterwards  lose  their  tubular 
form  and  continue,  in  the  opinion  of  most  histologists,  not  in 
the  usual  way  by  a  closed  capillary  network  into  the  veins, 


548 


PHYSIOLOGY 


CHAP. 


but  by  opening  freely  into  the  labyrinthine  spaces  of  the  splenic 
reticulum.  From  the  same  reticulum  the  roots  of  the  small  veins 
(see  Fig.  260)  arise  by  an  opposite  process  and  then  open  into 
those  which  course  along  the  trabeculae. 

The  lymphatics  of  the  spleen  form  plexuses  in  the  capsule  and 
in  the  trabeculae.  They  are  not  very  numerous,  and  run  with 
the  arteries,  sometimes  surrounding  them,  to  form  a  plexus.  The 
perivascular  adenoid  tissue  and  the  follicles  composed  of  the 
Malpighian  nodules  communicate  with  the  lymphatic  vessels  with 


FIG.  26^. — Section  of  Malpighian  corpuscle  and  surrounding  tissue  of  splenic  pulp,  with  injected 
network  of  blood  capillaries,  treated  with  silver  chromate  ;  highly  magnified.  (Oppel.)  1, 
.Malpighian  corpuscle ;  -2,  part  of  its  reticulum  ;  3,  denser  reticulum  at  the  edge  of  the 
corpuscle  ;  4,  looser  tissue  external  to  the  former  ;  5,  (»,  connective  tissue  of  arterial  sheath, 
to  which  the  corpuscle  is  adhering ;  7,  capillaries  of  corpuscle  ;  8,  reticulum  of  pulp  surround- 
ing the  arteriole. 

proper  walls  that  run  in  the  tissue  of  the  trabeculae.     All  the 
lymphatics  issue  from  the  hilum  together  with  the  blood-vessels, 
and  then  join  the  lymphatic  ganglia  of  the  posterior  part  of  the 
'abdomen. 

rf'tfcr  The  nerves  of  the  spleen  are  derived  from  the  solar  plexus ; 
f  hey  enter  by  the  hilum  along  with  the  vessels.  They  are  certainly 
in  peripheral  relation  both  wjth  the  muscle  cells  of  the  vessels  and 
with  those  of  the  capsule  ancl  trabeculae.  Their  central  origin  is 
probably  in  the  bull)  and  cervical  tract  of  the  spinal  cord.  In 
order  to  reach  the  periphery,  the  splenic  nerves  pass  by  the  left 


XIV 


THE  LYMPH 


549 


splanchnic  and  semilunar  ganglion,  from  which  arises  the  splenic 
plexus. 

According  to  the  histological  researches  of  Retzius,  v.  Kolliker, 
and  Fusari,  the  nerves  of  the  spleen  are  usually  non-niedullated 
and  for  the  most  part  supply  the  vascular  muscles. 

From  the  above  it  is  evident  that  the  blood  which  penetrates 
the  spleen  by  the  splenic  artery  comes  into  immediate  relation  with 
the  elements  of  the  splenic  pulp  contained  in  the  labyrinthine 
spaces,  and  that  the  blood  which  issues  from  the  spleen  by  the 
splenic  vein  must  have  traversed  the  lacunar  system. 

On  examining  the  mobile  elements  of  the  splenic  pulp  undei 
the  microscope,  they  are  seen  to  consist  for  the  most  part  of 
erythrocytes  and  leucocytes,  i.e.  of  the  corpuscles  of  normal  blood, 
which,  owing  to  the  marked  circulatory  delay  within  the  lacunar 
system,  become  concentrated  with  very  little  plasma. 

Besides  the  ordinary  red  and  white  blood-corpuscles,  however, 


FKJ.  '2<>3. — Splenic  cells  of  various  forms  and  sizes,  containing  in  tlieir  cytoplasm  pigment 
granules,  and  erythrocytes  in  process  of  dissolution,  or  fragments  of  already  dissolved 
erythrocytes  :  magnification  of  1'JCO  diameters.  (From  a  dry  preparation  of  F.  Miiller.) 

the  splenic  pulp  contains  other  elements,  similar  to  those  of  bone 
marrow.  Megacaryocytes  are  rare,  at  least  in  man  ;  on  the  other 
hand,  there  is  an  abundance  of  smaller  amoeboid  cells  (although 
still  twice  the  size  of  common  leucocytes),  many  of  which  exhibit 
erythrocytes  in  process  of  breaking  up  (globuliferous  splenic  cells) 
inside  them.  There  are  many  intermediate  forms  between  the 
ordinary  leucocytes  and  the  globuliferous  cells,  all  containing  in 
their  protoplasm  extraneous  corpuscles  of  varying  form  and 
magnitude,  which  represent  pigment  granules  or  the  detritus  of 
erythrocytes  ingested  by  phagocytes  (Kolliker  and  Ecker;  Fig. 
263).  The  plasma,  again,  in  which  these  amoeboid  cells  are 
suspended,  contains,  in  addition  to  the  normal  erythrocytes^'a 
certain  number  of  red  corpuscles  which  are  at  different  stages*  oT 
disruption,  and  pigment  granules  Derived  from  the  decomposition 
of  haemoglobin. 

In  the  spleen  of  very  young  animals,  there  are  constantly 
present  along  with  the  erythrocytes  a  greater  or  less  number  of 
erythroblasts  or  nucleated  red  corpuscles  in  various  stages  of 


550  PHYSIOLOGY  CHAV. 

development  (Funke  and  Kolliker)-  In  adult  animals,  too,  after 
repeated  bleedings,  Bizzozero  and  Salvioli  noted  the  appearance 
of  haematoblasts,  which  are  absent  under  ordinary  conditions 
(Neumann). 

In  view  of  these  facts,  and  of  what  has  been  stated  in  regard  to 
the  functions  of  bone  marrow,  we  cannot  doubt  that  the  spleen  is  a 
haemopoietic  and  haemolytic  organ.  Its  haemopoietic  function, 
as  demonstrated  by  the  presence  of  the  erythroblasts,  seems  to  be 
very  active  during  intra- uterine  life,  when  the  oone  marrow 
contains  the  fewest  number  of  nucleated  red  corpuscles  ;  it  is 
greatly  reduced  in  the  first  period  of  extra-uterine  life,  when  the 
haemopoietic  function  of  bone  marrow  increases ;  it  is  abolished  in 
adults,  in  whom  bone  marrow  functions  in  full  activity ;  lastly,  it 
recurs  in  adults  under  circumstances  in  which  the  body  requires  a 
hurried  neo-forrnation  of  the  cytological  elements  of  the  blood. 

That  the  spleen  is  not  an  effective  haemopoietic  organ  in  adult 
animals  has  been  conclusively  demonstrated  by  the  recent  work  of 
Faton,  Gulland,  and  'Fowler  (1902)  on  dogs,  cats,  and  rabbits. 

These  authors  employed  four  different  methods  of  research :  (a) 
comparison  of  the  number  of  blood-corpuscles  present  in  the  splenic 
artery  or  carotid  with  the  number  of  corpuscles  present  in  the 
splenic  vein ;  (&)  determination  of  the  effects  on  the  blood- 
corpuscles  of  extirpation  of  the  spleen ;  (c)  measurement  of  the 
time  it  takes  in  normal  and  a-splenic  animals  to  regain  the  normal 
mass  of  corpuscles  either  after  haemorrhage  or  after  the  action  of 
haemolytic  agents;  (d)  study  of  the  action  on  haematopoiesis 
of  injections  of  splenic  extract.  The  following  results  were 
obtained  :— 

In  dogs  and  cats  no  difference  was  observed  either  in  the 
number  or  character  of  the  erythrocytes  in  the  blood  that  goes  to 
the  spleen,  as  compared  with  the  blood  that  flows  out  from  the 
spleen.  It  appears,  however,  that  there  is  a  slight  reduction  in  the 
number  of  the  leucocytes,  more  particularly  in  that  of  the  poly- 
nucleated. 

Extirpation  of  the  spleen  in  dogs,  cats,  and  rabbits  has  no 
, apparent  effect  on  the  number  of  erythrocytes,  nor  upon  the  protein 
components  of  the  blood  plasma  (at  least  in  dogs).  There  appears, 
however,  to  be  a  slight  reduction  of  the  eosinophile  leucocytes. 
After  haemorrhage  in  rabbits,  and  haemolysis  in  dogs,  the  normal 
number  of  erythrocytes  is  restored  in  the  same  time,  both  in  the 
control  animals  and  in  those  which  have  lost  their  spleen.  Injection 
of  splenic  extract  does  not  produce  any  augmentation  in  the 
number  of  erythrocytes  in  the  rabbit,  but  they  do  increase,  on  the 
contrary,  after  injection  of  extract  of  red  bone  marrow. 

From  the  above  data  the  authors  conclude  that  they  have  not 
established  any  fact  to  prove  that  the  spleen  possesses  a  haemo- 
poietic function. 


xiv  THE  LYMPH  551 

The  haemolytic  function  of  the  spleen  may  be  argued  from 
the  numerous  phagocytes  in  various  stages  of  development,  the 
erythrocytes  in  process  of  destruction,  and  the  pigment  granules 
contained  in  the  plasma  of  the  splenic  pulp.  Analysis  of  the 
chemical  constituents  of  the  spleen,  moreover,  make  it  probable 
that  this  organ  is  the  seat  of  highly  complex  metabolic  processes 
involving  the  destruction  of  many  corpuscles. 

According,  however,  to  the  latest  work  on  dogs,  cats,  and 
rabbits  by  Paton  and  Goodall  (1903),  it  appears  that  the  spleen  has 
no  genuine  and  proper  haemolytic  function  ;  but  that  its  work  is 
confined  to  the  taking  up  of  erythrocytes  that  are  already  dead, 
and  the  chemical  transformation  of  their  pigment,  by  storing  up 
the  iron,  which  can  then  be  utilised  for  the  formation  of  other 
erythrocytes. 

On  the  other  hand,  W.  Bain  (1903),  by  artificially  circulating 
the  isolated  spleen  and  liver  of  dog,  with  the  object 'of  determining 
the  importance  of  these  two  organs  in  haemolytic  processes,  came 
to  the  conclusion  that  both  spleen  and  liver,  under  these  con- 
ditions of  survival,  exhibit  the  property  of  destroying  erythrocytes 
as  well  as  leucocytes.  The  spleen  acts  principally  upon  the 
leucocytes,  among  which  it  more  particularly  attacks  those  with 
polymorphous  nuclei,  although  a  certain  quantity  of  erythrocytes 
(2'4  per  cent)  are  also  destroyed. 

Besides  the  chemical  compounds  present  in  these  highly 
vascular  organs,  there  are  other  special  products  in  the  splenic 
pulp.  One  of  the  most  important  is  a  ferric  albuminate  which 
certainly  depends  on  the  chemical  changes  of  the  haemoglobin  in 
the  erythrocytes  broken  up  by  the  spleen.  The  large  amount  of 
iron  that  can  be  recovered  from  the  spleen  has  led  some  observers 
to  consider  that  it  is  a  storehouse  of  iron  destined  to  the  formation 
of  new  haemoglobin. 

A  series  of  recent  researches  by  Tedeschi  (1899)  confirms  the 
fact  already  admitted  by  Kriiger  and  Lapicque  to  the  effect  that 
the  spleen  is  an  organ  rich  in  iron ;  that  on  an  average  there  is 
less  in  young  than  in  adult  rabbits ;  and  that  it  seems  to 
diminish  again  in  old  age.  This  excess  of  iron  in  the  spleen  is 
probably  derived  from  decomposition  of  the  haemoglobin  of  the 
erythrocytes  broken  up  in  the  spleen.  This  does  not,  however, 
forbid  the  assumption  that  part  at  least  of  these  organic  iron 
compounds  may  serve  the  erythrocytes  that  pass  through  the 
spleen  as  materials  for  the  construction  of  new  haemoglobin. 
Arguments,  in  fact,  are  not  wanting  to  show  that  the  haemoglobin 
contained  in  the  erythrocytes  of  the  venous  blood  that  leaves  the 
spleen  is  in  excess  of  that  contained  in  the  erythrocytes  of  the 
arterial  blood  that  enters  it ;  consequently  the  spleen  must 
take  an  active  part  in  the  formation  of  haemoglobin  and  the 
maturation  of  the  red  corpuscles  of  the  blood.  This  is  indicated 


552  PHYSIOLOGY  CHAP. 

particularly  from  the  work  of  Gurwitsch  (1893)  and  Zelensky 
(1891).  The  former  made  10  minute  comparative  analyses  of  the 
blood  of  the  carotid  and  splenic  vein  in  dogs ;  the  latter  determined 
on  dogs  and  rabbits  the  effect  of  the  peritoneal  injection  of  splenic 
extract.  On  counting  the  corpuscles  and  estimating  the  haemo- 
globin with  Hiifner's  spectro-photoineter,  before  and  after  injection, 
there  was  invariably  a  marked  rise  in  both,  whence  the  author 
concluded  that  "  splenic  infusion  contains  the  products  necessary 
to  the  regeneration  of  the  blood." 

The  lymphoid  tissue  of  the  spleen,  which  consists  essentially  of 
Malpighian  corpuscles  or  nodules,  is  a  lymphapoietic  or  leucocyte- 
forming  organ  analogous  to  the  lymph  follicles  and  glands 
(Virchow).  This  is  plain  from  the  fact  that  the  blood  of  the 
splenic  vein  contains  many  more  leucocytes  than  the  blood  of  the 
splenic  artery  (Kolliker  and  Hirt,  Bizzozero  and  Salvioli).  In  the 
blood  of  the  splenic  vein  the  ratio  between  the  number  of  the 
leucocytes  and  that  of  the  erythrocytes  is  as  1 : 60 ;  in  the 
arterial  blood,  as  1  : 2260.  In  splenic  leucaemia  the  lympha- 
poietic function  of  the  spleen  is  enormously  increased,  so  that  it 
sends  out  a  great  quantity  of  leucocytes  into  the  blood  torrent. 
This  fact  coincides  with  a  corresponding  enlargement  of  the  organ, 
due  to  hyperplasia  of  the  lymphoid  tissue. 

It  is  to  the  wealth  of  leucocytes  in  the  spleen  and  their 
special  metabolism  that  we  must  refer  the  fact  that  the  chemical 
compounds  of  the  splenic  pulp  abound  in  nuclein  and  its  deriva- 
tives, i.e.  adenine,  xanthine,  hypoxanthine,  guanine,  and  uric  acid. 
Lecithin,  jecorin,  cholesterin,  and  inosite  are  also  present.  The 
alkaline  reaction  of  the  splenic  pulp  becomes  acid  after  a  short 
time,  owing  to  the  development  of  fatty  acids,  among  which  are 
succinic,  formic,  acetic,  and  lactic  acid.  The  constant  presence  of 
uric  acid  in  the  fresh  spleen  should  be  noted,  even  in  these 
herbivorous  animals  whose  urine  does  not  contain  it.  Horbaczewski 
(1889)  states  that  when  a  fragment  of  still  living  spleen  is  dipped 
into  blood  freshly  extracted  from  an  animal,  it  induces  the  forma 
tion  of  considerable  quantities  of  uric  acid.  This  proves  the  spleen 
to  be  an  important,  if  not  the  sole,  organ  in  the  formation  of  uric 
acid,  which,  as  we  shall  see  elsewhere,  is  derived  from  the  nuclein 
bases  present  in  large  quantities  in  the  splenic  pulp. 

Since  the  spleen  is  a  contractile  organ,  its  volume  undergoes 
great  variations.  Normally  it  swells  during  the  digestive  period, 
reaching  its  maximum  five  hours  after  meals ;  it  remains  turgid 
for  some  time,  and  eventually  regains  its  normal  volume.  This  is 
the  effect  of  an  active  hyperaemia  analogous  to  that  which  is 
simultaneously  exhibited  by  the  mucosa  of  the  alimentary  cord,  the 
pancreas,  and  the  other  glands  attached  to  the  digestive  apparatus. 
This  coincidence  in  hyperaemia  points  to  the  probability  of  the 
active  intervention  of  the  spleen  in  the  chemical  phenomena  of 


xiv  THE  LYMPH  553 

the  digestive  secretion.  It  seems  probable,  in  fact,  from  the 
theoretical  standpoint  that  the  congested  spleen,  by  means  of  the 
nutritive  substances  freshly  absorbed  from  the  digestive  apparatus, 
produces  and  pours  into  the  blood  substances  that  favour  in  some 
way  the  formation  of  the  enzymes  which  are  the  active  principles 
of  the  gastric  (Baccelli)  or  of  the  pancreatic  juice  (Schiff,  Herzeii). 
We  shall  return  to  this  point  iu  another  connection.  It  also 
appears  highly  probable  that  the  spleen  and  perhaps  the  lymphoid 
organs  and  tissues  in  general  serve  as  magazines  or  reserve  stores 
for  the  proteins  deriving  from  digestion,  and  which  cannot  be 
immediately  utilised  by  the  tissues,  just  as  the  liver  stores  up  the 
carbohydrates  that  accumulated  there,  in  the  form  of  glycogen.  In 
favour  of  this  hypothesis  we  have  the  fact  of  the  marked  reduction 
which  the  spleen  and  lymph  glands  undergo  during  inanition 
(Fredericq). 

Another  important  phenomenon  observed  in  clinical  practice  is 
the  temporary  swelling  exhibited  by  the  spleen  in  many  of  the 
infective  diseases  that  are  accompanied  by  fever.  In  malarial 
fevers  the  enlargement  of  the  spleen  increases  constantly,  with 
repeated  attacks,  until  it  becomes  permanent  and  may  reach 
considerable  proportions,  either  by  the  accumulation  of  the 
malarial  parasites  and  their  products,  or,  as  is  probable,  by 
paralysis  of  all  the  muscular  elements  of  the  organ.  We  have 
seen  that  the  lymphatic  glands  swell  by  a  similar  process  under 
similar  morbid  conditions,  and  that  this  process  is  of  great  import- 
ance in  arresting  the  infective  germs,  and  rendering  the  toxic 
substances  which  they  produce  innocuous.  The  spleen  may  also 
be  regarded  as  an  organ  of  defence  against  infective  agents,  which 
harmonises  perfectly  with  the  fact  of  the  presence  of  numerous 
phagocytes  contained  in  the  splenic  pulp. 

The  contractility  of  the  spleen  has  been  tested  by  direct  stimula- 
tion of  the  organ,  and  by  excitation  of  the  peripheral  nerves  that 
run  to  it,  as  also  by  direct  or  reflex  stimulation  of  the  nerve  centres. 

If  the  spleen  of  an  anaesthetised  dog  is  exposed,  the  contact 
of  the  air  at  first  produces  a  contraction  of  the  organ,  which 
disappears  after  some  time,  its  surface  becoming  supple  again,  and 
dark  red.  On  then  bringing  together  the  electrodes  from  an 
induction  coil  and  applying  them  to  any  point  on  the  organ,  a 
hollow  and  blanching  will  be  produced  in  consequence  of  local 
contraction,  which  drives  out  the  blood.  On  running  the 
electrodes  over  the  surface  of  the  organ,  grooves  and  white  lines  of 
any  form  desired  can  be  traced  (Briicke).  The  human  spleen  has 
less  contractility  than  that  of  the  dog,  cat,  and  many  other 
animals,  owing  to  the  smaller  number  of  muscle  cells  contained  in 
the  capsule  and  the  trabeculae;  contraction  can,  however,  be 
determined  by  the  percussion  method,  after  faradisation  of  the 
organ  through  the  skin  (Botkin). 


554  PHYSIOLOGY  CHAP. 

Koy  was  able  by  the  plethysinographic  method,  ingeniously 
modified  and  applied  to  the  spleen  in  situ,  to  study  the  automatic 
variations  in  volume  of  this  organ.  He  snowed  that  the  spleen  6f 
dogs  and  cats  presents  periodic  contractions  and  expansions 
lasting  in  all  for  about  a  minute,  independent  of  the  slow 
oscillations  of  arterial  pressure,  and  therefore  of  the  dilatations 
and  constrictions  of  the  arteries,  which  must  accordingly  be 
referred  to  the  periodic  contractions  and  expansions  of  the  muscle 
cells  of  the  capsule  and  trabeculae.  The  spleen  of  these  animals 
is  therefore  a  muscular  organ  which  rhythmically  expands  to 
receive  an  increased  amount  of  blood,  and  rhythmically  contracts 
to  expel  a  considerable  part  of  the  blood  which  it  contains,  in  the 
direction  of  the  liver.  During  its  expansion  the  blood  which  has 
been  driven  out  into  the  reticuluni  of  the  splenic  pulp,  and  is  at 
rest  there,  probably  undergoes  important  metabolic  changes; 
during  contraction  the  blood  whicli  has  suffered  these  changes, 
and  many  of  the  mobile  elements  that  lodge  in  the  areoli 
containing  the  pulp,  and  the  follicular  tissue  of  the  Malpighian 
corpuscles,  are  driven  out  through  the  efferent  vessels  of  the 
organ. 

The  muscular  activity  of  the  spleen,  whether  of  the  muscles  of 
the  capsule  and  trabeculae  or  of  the  vessels,  is  regulated  and 
controlled  by  the  nervous  system.  A  pronounced  and  more  or 
less  rapid  contraction  of  the  spleen  can  be  obtained  by  the 
electrical  excitation  of  the  spinal  bulb,  the  upper  cervical  cord, 
left  splanchnic,  semilunar  ganglion,  and  lastly  the  nerve  plexus  to 
the  spleen  (Tarchanoff).  The  same  effect  can  be  obtained  reflexly 
by  the  electrical  excitation  of  a  sensory  nerve  or  of  the  central 
end  of  the  vagus.  The  contraction  of  this  organ  during  asphyxia 
(as  also  in  strychnine  or  strong  quinine  poisoning)  is  also  due 
to  excitation  of  the  nervous  system,  which  governs  the  muscles  of 
the  spleen.  Section  of  the  splenic  nerves  or  their  paralysis  from 
any  cause  induces  the  opposite  effects,  i.e.  the  passive  enlargement 
of  the  organ. 

According  to  Bulgak  (1877),  the  reflex  and  motor  centres  for 
the  muscles  of  the  spleen  lie  in  the  cord  between  the  first  and 
fourth  cervical  vertebra,  while  lower  down,  as  far  as  the  eleventh 
dorsal  vertebra,  there  are  only  the  afferent  and  efferent  nerve 
fibres  to  the  spleen.  Schafer  and  Moore  substantially  confirmed 
these  results. 

In  view  of  the  marked  difference  in  volume  which  the  spleen 
exhibits  owing  merely  to  fluctuation  in  the  amount  of  blood  that 
collects  in  it,  certain  physiologists,  including  Briicke,  have  looked 
upon  it  as  a  diverticulum  capable  of  modifying  or  influencing  the 
circulation  of  the  other  abdominal  organs,  notably  the  stomach 
and  the  liver,  in  various  ways.  This  idea  is  founded  on  the 
anatomical  fact  that  the  splenic  artery  and  the  gastric  and 


xiv  THE  LYMPH  555 

hepatic  coronaries  are  three  branches  of  one  trunk,  the  coeliac 
artery,  and  that  in  proportion,  as  the  inflow  of  blood  through  the 
splenic  artery  is  easy  or  difficult,  the  blood  supply  to  the  stomach 
and  liver  must  diminish  or  increase.  Drosdotf  and  Botschet- 
schkaroff  saw  by  direct  observation  that  the  contraction  of  the 
spleen  induces  increased  blood  supply  to  the  liver.  On  stimulating 
the  previously  divided  nerves  of  the  splenic  plexus,  and  thus 
producing  a  marked  contraction  of  the  spleen,  the  amount  of 
blood  that  flows  from  a  puncture  previously  made  on  the  surface 
of  the  liver  is  conspicuously  increased. 

Little  has  been  added  to  these  positive  data  in  regard  to 
the  various  physiological  functions  of  the  spleen,  from  the  results 
of  the  recent  methodical  researches  on  the  consequences  of  its 
extirpation.  Galen  and  Pliny  were  already  aware  that  the  spleen 
can  be  excised  without  danger  to  the  animal.  The  first  splenectomy 
performed  on  man  was  by  Zaccarelli,  in  1549.  Morgagni  mentions 
a  woman  whose  spleen  was  removed  in  consequence  of  its  protrusion 
from  an  abdominal  wound,  and  who  survived  the  operation  for 
five  years,  and  subsequently  became  a  mother. 

Innumerable  experiments  have  been  made  in  this  direction, 
and  there  is  probably  no  physiologist  who  has  not  successfully 
attempted  the  extirpation  of  the  spleen  at  various  times,  either  on 
dogs  or  rabbits.  After  the  introduction  of  antiseptics,  many 
surgeons  performed  the  operation  on  man  with  a  therapeutic 
object.  Its  want  of  success  in  cases  of  leucaemia,  of  amyloid 
degeneration,  and  of  circulatory  stasis  in  the  organ  is  no  evidence 
that  the  spleen  is  essential  to  human  life,  while  the  many 
successful  operations  (66  per  cent,  according  to  Vulpius)  in  cases 
of  wandering  spleen,  simple  hypertrophy,  suppuration,  cysts, 
sarcomata,  etc.,  show,  on  the  contrary,  that  it  is  possible  to  sur- 
vive splenectomy  with  no  ill  consequences,  provided  other  serious 
lesions  are  not  present. 

Not  merely  can  animals  resist  splenectomy,  but  it  has  been 
demonstrated  by  the  experiments  of  Tizzoni  (1884)  on  rabbits, 
of  Kurlow  (1862)  on  guinea-pigs,  of  Dastre  (1893)  on  young- 
puppies,  kittens,  guinea-pigs,  and  mice  that  this  operation  neither 
perceptibly  retards  development,  nor  does  it  impair  the  repro- 
ductive capacity. 

On  counting  the  blood-corpuscles  before  and  after  splenectomy 
in  dogs  (Emelianow,  1893),  rabbits,  and  goats  (Vulpius,  1894), 
a  relative  diminution  of  erythrocytes  and  increase  of  leucocytes 
has  been  observed.  The  same  fact  has  often  been  noted  in  regard 
to  man,  when  splenectomy  has  been  performed,  especially  in  the 
cases  referred  to  by  Crede,  Kocher,  Severanu,  and  Czerny.  This 
is  the  only  fact  that  could  be  invoked  in  support  of  the  theory 
that  many  leucocytes  are  transformed  into  erythrocytes  in  the 
spleen,  by  taking  up  or  forming  haemoglobin,  with  expulsion  of 


556  PHYSIOLOGY  .  CHAP. 

the  nucleus  or  its  atrophy  and  reabsorption.  We  have  'seen, 
however,  that  this  theory  was  contradicted  by  microscopical 
observations  of  the  mobile  elements  of  the  splenic  pulp,  among 
which  there  are  normally  no  erythroblasts  nor  other  transitional 
forms  between  leucocytes  and  erythrocytes.  On  the  other  hand, 
the  observations  of  Vulpius  show  that  after  at  most  nine  weeks 
after  splenectomy  it  is  impossible  to  recognise  any  difference 
between  the  blood-corpuscles  of  normal  and  those  of  a-splenic 
animals,  showing  that  the  lymphapoietic-or  haemapoietic  function 
of  this  organ  is  readily  replaced  by  either  the  lymphatic  glands 
or  the  bone  marrow.  It  is  apparently  in  this  sense  that  we  should 
interpret  the  more  recent  negative  results  obtained  by  Paton  and 
Gulland,  and  Fowler,  as  above  cited. 

Hypertrophy  of  the  lymphatic  glands  after  splenectomy  has 
been  repeatedly  observed  on  animals  as  well  as  man ;  but  the 
effect  is  not  constant,  nor  is  it  of  long  duration,  which  leads  one  to 
suppose  that  it  is  the  result  of  the  operative  procedure.  Even 
without  any  striking  hypertrophy,  however,  it  may  be  assumed 
that  the  lymphatic  glands,  which  are  exceedingly  numerous,  are 
capable  of  vicariously  assuming  the  lapsed  functions  of  the  spleen. 

Bone  marrow  sometimes  seems  to  contain  a  large  number  of 
haematoblasts  after  splenectomy  (Litten  and  Orth,  Emelianow); 
in  a-splenic  rabbits  and  guinea-pigs  it  contains  more  iron  than  in 
intact  animals  of  the  same  age  (Tedeschi,  1899).  This  functional 
substitution  is  not,  however,  always  apparent,  nor  in  any  case  is  it 
indispensable,  since  in  fishes  which  have  no  bone  splenectomy  is 
supported  without  any  perceptible  alteration  of  the  blood-corpuscles 
(Pouchet,- 1878). 

Certain  observations  exist  which  tend  to  show  that  the  functions 
of  the  spleen  can  be  partly  taken  on  by  the  liver.  Maggiorani 
(1862)  stated  that  the  weight  of  the  rabbit's  liver  in  splenectoniised 
rabbits  exceeded  that  of  intact  rabbits  by  about  f ;  Montenovesi 
(1893)  describes  a  clinical  case  of  hypertrophy  of  the  liver  con- 
sequent on  splenectomy ;  lastly,  Tedeschi  (1899)  has  recently 
shown  that  the  liver  of  the  a-splenic  rabbit  contains  a  larger 
average  amount  of  iron  than  the  liver  of  intact  rabbits,  young  or 
old.  Still  these  facts  do  not  seem  to  us  sufficiently  conclusive  to 
admit  of  our  assuming  that  the  liver  undergoes  such  modifications 
as  would  enable  it  to  resume  the  haemopoietic  functions  which  it 
performs  during  the  embryonic  life.  The  increase  in  volume  and 
weigHt  of  the  liver  after  splenectomy,  as  also  the  increased  wealth 
of  iron,  may  depend  on  a  more  copious  blood  supply;  also,  as  rightly 
suggested  by  Maffucci,  on  the  fact  that  this  organ,  after  splenectomy 
for  malarial  hypertrophy,  becomes  the  principal  repository  for 
parasites  and  malarial  pigments. 

It  has  been  maintained  that  the  spleen,  after  total  extirpation, 
is  reproduced  or  regenerated  in  the  form  of  one  or  more  lesser 


xiv  THE  LYMPH  557 

spleens  that  did  not  exist  previous  to  the  operation  (Vella, 
Tizzoni).  But  it  was  subsequently  discovered  that  there  are  not 
seldom  nodules  of  a  substance  analogous  to  that  of  the  spleen  in 
its  immediate  neighbourhood,  in  the  gastro-splenic  omen  turn  and 
great  omentum,  which  represent  true  accessory  or  supernumerary 
spleens,  and  these  after  the  operation  may  become  more  developed 
(Foa).  It  has  also  been  demonstrated  that  if  in  the  act  of  excising 
the  spleen  some  of  the  splenic  pulp  is  scattered  in  the  omentum, 
it  is  capable  of  lodging  there  and  giving  rise  to  the  formation  of 
lesser  spleens  that  did  not  previously  exist  (Cecchini  and  Grimni). 
In  no  case  could  the  capacity  of  lymphoid  splenic  tissue  to  lodge 
and  reproduce  itself  be  invoked  in  favour  of  the  theory  that 
the  spleen  is  an  organ  indispensable  to  life.  Whatever  the 
importance  of  its  functions,  they  may  easily  be  replaced  by  the 
other  lymphoid  tissues  which  abound  in  the  body. 

Lastly,  we  must  remark  that  of  late  years  special  modifications 
of  the  lymphatic  glands  have  been  described  under  the  name  of 
haemolymphatic  glands  (Leydig,  Gibbes,  Kobertsou,  Drummond, 
Vincent  and  Harrison,  Weidenreich).  They  are  found  along  the 
whole  length  of  the  aorta,  and  are  differentiated  from  the  ordinary 
lymph  glands  by  the  fact  that  no  lymphatic  vessels  can  be 
demonstrated  in  them.  Both  sinus  and  the  vessels  are  filled  with 
blood  instead  of  lymph.  According  to  their  histological  structure, 
they  must  represent  a  connecting  link  between  the  ordinary 
lymphatic  glands  and  the  spleen  (Vincent  and  Harrison).  In  all 
probability  their  function  is  analogous  to  that  of  the  other 
haeinopoietic  organs  (Seemann,  1904). 

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Physiol.,  1909-10,  xxv.  345-53. 

H.  O.  LTJSSKY.  Contributions  to  the  Physiology  of  Lymph.  Amer.  Journ.  of 
.Physiol.,  1909-10,  xxv.  354-66. 


INDEX    OF    SUBJECTS 


Abdominal  respiration,  416 
Absorption  of  gases,  378 
Acapnia,  474 
Accelerators,  heart,  327 
Accessorius,  nerve,  328 
Acid,  aereal,  373 

amino-iso-valerianic,  27 

aspartic,  27,  129 

butyric,  37 

caproic,  35 

carbonic,  blood,  380,  385,  397 

carbonic,  discovery,  373 

carbonic,  expired  air,  389,  395 

diamino-trioxy-dodecanic,  27 

glutamic,  27 

hippuric,  129 

lactic,  plasma,  130 

lactic,  urine,  470 

laevulinic,  24 

nucleic,  24,  138 

oleic,  35 

oxalic,  60 

oxypyrrolidine-carboxylic,  27 

palmitic,  35 

a-pyrrolidine-carboxylic,  27 

stearic,  35 

uric,  129,  552 

valerianic,  35 
Acid  albumin,  23 
Actinosphaerium  Eichhornii,  74 
Adaptation,  49,  63,  65 

of  respiration,  469 
Adenase,  33 
Adenine,  24,  33,  35 
Adynamia  cordis,  333 
Aerobic  organisms,  68 
Aerotonometer,  388,  490 
Afferent  nerves,  heart,  333 

nerves,  respiration,  457,  464 
Agminated  follicles,  530 
Air,  alveolar,  390 

complemental,  423 

expired,  397 

inspired,  397 

reserve,  423 

residual,  423 

tidal,  423 

VOL.  I 


1    Ala  cinerea,  445 
Alanine,  23,  27 
Alanyl-glycine,  23 
Alanyl-leucine,  23 
Albuminate,  ferric,  spleen,  551 
Albuminoids,  23 
Albumoids,  25 
Albumose,  23 
Alcoholase,  34 
Aleuron,  18 
Alexines,  154 
Alkali  albumin,  23 
Alkalimetry,  blood,  96 
"All  or  nothing,"  318 
Allonomous  metabolism,  87 
Allorhythmia  cordis,  316 
Alveolar  air,  390 

pressure,  405 
Alveoli,  pulmonary,  403 
Amoeba,  14 
Amoeboid  movement,  74 

movement,  leucocytes,  115 
Amino-acids,  27,  129 
Ammonia,  plasma,  129 
Amylase,  33 
Amyloid,  25 
Amylopsin,  33 
Anabiosis,  66 
Anabolism,  43,  46,  57,  68 

vagus,  332 
Anaemia,  100 

pernicious,  539 
Anaerobic  organisms,  68 
Anaesthetics,  53  , 
Anelectrolytes,  142 
Anhydraemia,  143 
Animal  gum,  130 
Animals,  characters,  19,  53 
Annulus  of  Vieussens,  328,  354 
Anterolateral  nucleus,  363 
Anti-coagulants,  124 
Anti-kinase,  blood,  128,  140 
A  nti- thrombi  n,  140 
Aorta,  pressure,  208 
Apex  beat,  221 
Apnoea,  birds,  484 

experimental,  475 

2  o 


561 


562 


PHYSIOLOGY 


Apnoea,  foetal,  477 

true  and  false,  477 

vagi,  479,  488 

voluntary,  480 
Arginase,  33 
Arginine,  27,  33 
Argon,  blood,  387 
Arteria  aspera,  159 

venosa,  159 
Arterial  pressure,  241,  243,  253 

pressure,  pulmonary,  254 

pulse,  263 

tone,  346 
Arteries,  locomotion,  245,  277 

pressure,  241,  243,  253 

suspension,  245 

tone,  346 

velocity  in,  256 
Asparagine,  60 
Asphyxia,  380,  469 
Aspiration,  diastolic,  208,  210 

systolic,  208 
Assimilation,  86 
Atelectasis,  405 
Atmosphere,  gases,  397 
Atmospheric  pressure,  72 
Atropine,  secretion,  522 
Auditory  nerve,  respiration,  465 
Auricles,  180 

pressure  in,  203 

septum,  299 
Auriculo-ventricular  bundle,  315 

valves,  192 
Auscultation,  heart,  196 

lungs,  426 
Autolysis,  34 
Automatic  control,  heart,  210 

respiration,  461 
Automaticity,  heart,  298,  305 

respiration.  457,  480 

vascular  rhythm,  343 

vital,  83,  85 

Autonomous  metabolism,  86 
Autosphygmogram,  265 
Auxocardia,  186,  215,  226 

Bacillus  butyricus,  37 
Bacteria,  metabolism,  61,  65 

nitrifying,  58 
Bacteriolysis,  154 
Bacterium  lacticum,  37 

photometricum,  78 
Barometric  pressure,  blood,  384 

respiration,  474 
Barotaxis,  76 
Bathmotropism,  327 
Benthos,  82 
Bilirubin,  109 
Biogen  hypothesis,  88 
Biogenesis,  2 
Biology,  scope    1 

marine,    81 
Biometry,  48 


Biomorphosis,  49 
Biotouus,  88 
Biuret  test,  22 
Blood,  alexines,  154 

alkalimetry,  96 

asphyxia,  380 

bactericidal  properties,  154 

bufFy  coat,  97 

circulation,  157 

coagulation,  97,  132 

corpuscles,  91,  100,  113,  117 

defibrinated,  97 

enzymes,  127 

erythrocytes,  100 

examination,  120 

gases,  132,  379,  384,  388,  474 

immunity,  154 

leucocytes,  113 

lymph,  512 

metabolites,  129 

peptone,  124 

physical  properties,  94 

plasma,  123 

platelets,  117 

pressure,  238,  281 

pressure  in  arteries,  241 

pressure  in  capillaries,  253 

pressure  in  veins,  253 

quantity,  98 

reaction,  94 

respiratory  rhythm,  490 

specific  gravity,  95 

spectra,  110 

stream,  232 

toxicity,  153 

transfusion,  152 

velocity  in  arteries,  256,  261 

velocity  in  capillaries,  263,  281 

velocity  in  veins,  262,  281 

vessels,  343 

viscosity,  151 
"Blut-schatten,"  106 
Bridge,  Wheatstone's,  150 
Bronchi,  403 
Bronchial  murmur,  427 

muscle  and  nerves,  442 
Buffy  coat,  97 
Bulbar  centres,  respiratory,  450 

vasomotor,  361 
Bulbus  arteriosus,  187 
Bundle,  auric ulo- ventricular,  314 
Butyric  fermentation,  37 

Calcium,  coagulation,  136 
Canaliculi,  lymphatic,  509 
Cannula,  perfusion,  288,  289 
Capacity,  vital,  423 
Capillaries,  blood,  172 

blood,  area,  263 

blood,  pressure,  253 

blood,  velocity  in,  263 

lymphatic,  507 
Caproic  acid,  35 


INDEX  OF  SUBJECTS 


563 


Carbohydrates,  36 

in  blood,  130 

metabolism,  59 

respiratory  quotient,  399 
Carbon  dioxide,  elimination,  391 

of  blood,  385 

output,  470 

Carboxy- haemoglobin,  110 
Cardiac  cycle,  205 

ganglia,  299 

muscle  and  nerves,  285 

nerves,  depressor,  360 

nerves,  sympathetic,  327 

nerves,  vagi,  322 

reflexes,  333 
Cardiograms,  223,  268 
Cardiograph,  222 
Cardio-pneumatic  movement,  227 
Caseinogen,  23,  40 
Caseose,  23 
Catalases,  34 
Catalysators,  31 
Catalysis,  31 

Catheter,  pulmonary,  388 
Cell,  8,  13,  16 

chemistry  of,  19,  20,  37 

colony,  15 

theory,  12 
Cells,  giant,  535 

marrow,  538 

splenic,  549 

Traube,  147 
Cellulose,  37 
Centres,  cardiac,  336 

expiratory  and  inspiratory,  454 

germinal,  529 

nerve,  oxygen,  394 

respiratory,  bulbar,  443 

respiratory,  cerebral,  452,  464 

respiratory,  spinal,  451 

splenic,  554 

vasomotor,  bulbar,  361 

vasomotor,  spinal,  362,  364 
Centrifuge,  98 
Centrosome,  13 
Cerebrin,  35 
Chemomorphosis,  49 
Chemotaxis,  74 

leucocytes,  178 
Chest,  cavity,  407 
Cheyne-Stokes  respiration,  492 
Chitin,  37 

Chloral,  respiration,  455 
Chlorophyll,  18,  58 
Chloroplasts,  59 
Cholesterin,  36,  130 
Chondrioderma,  16 
Chorda  tympani,  vasodilatation,  350 

tympani,  lymph,  522 
Chromoproteins,  23 
Chronotropism,  vagus,  325 
Chyle,  512 
Chymosin,  33,  128 


Circulation,  blood,  discovery,  157 

dynamics,  233 

intrathoracic  pressure,  406,  436 

lymph,  515 

time,  282 

Clostridium  Pasteurianum,  57 
Clupeine,  24 
Coagulation,  by  enzymes,  33 

by  heat,  21 

of  blood,  97,  132 

of  lymph,  513 

of  milk,  135 
Cocaine,  bulb,  450 

protoplasm,  102 
Collagen,  23,  25 
Colloids,  21 
Colpidium  colpoda,  66 
Complemental  air,  423 
Concentration,  molecular,  141 
Conchiolin,  25 

Conditions  of  activity,  heart.  292 
Conductivity,       electrical,       plasma, 

149 

Conjugated  proteins,  23 
Conservation,  of  energy,  5 

of  matter,  5 

Coronary  circulation,  210 
Corpora  Arantii,  187 
Corpuscles,  blood,  91,  100,  113 

lymph,  513 

Malpighian,  547 

marrow,  535 
Crassamentum,  97 
Creatine,  35,  129 
Creatinine,  35 
Crusta  phlogistica,  97 
Crying,  438 
Cryoscopy,  142,  148 
Crystalloids,  21 
Cube,  Schultz,  111 
Cycle,  cardiac,  180 
Cysteine,  27 
Cystine,  27 
Cytoglobulin,  140 
Cytoplasm,  13 
Cytosine,  24 

Darwinism,  47 
Death,  apparent,  66 
Delirium  cordis,  321 
Denaturation,  protein,  21 
Depressor  nerves,  333,  360 
Descent,  doctrine  of,  8 
Desiccation  and  revival,  66 
Deutoplasm,  35 
Dextrose,  36 

Diamino-trioxy-dodecanic  acid,  27 
Diapedesis,  115 
Diaphragm,  410,  417 
Diastases,  33 

blood,  127 
Diastole,  180,  208 

active,  208 


564 


PHYSIOLOGY 


Diastole,  aspiration,  208,  210 

vagal,  325 
Dicrotism,  265 
Differentiation,  91 
Diffusion,  gas,  378 
Digestion,  plant,  54 
Dilatator  nerves,  350 
Dionaea  nmscipula,  53 
Di-saccharides,  37 
Dissimilation,  86 
Dissociation,  ionic,  142 

oxyhaemoglobin,  395,  401 
Docimasia  hydrostatica,  405 
Dromorneters,  257 
Droinotropism,  sympathetic,  330 

vagal,  326 

Drosera  rotundi folia,  54 
Dualism,  6 

Duct,  thoracic,  506,  512 
Dynamics,  circulation,  233 
Dyspnoea,  403,  468 

compensatory,  480 

febrile,  469 

post-apnbeic,  481 

thermal,  470 

vagotomy,  458,  468 

venosity  of  blood,  469 

voluntary,  482 

Ear,  vasomotor  nerves,  343 
Ectoplasm,  17 
Eddies,  arterial,  189 
Effusions,  serous,  515 
Elastic  tubes,  flow,  239 
Elasticity,  blood-vessels,  239 
Elastin,  23,  25 
Electrical  conductivity,  149 

convection,  90 

stimuli,  80 

variations,  heart,  332 
Electrolytic  dissociation,  142 
Embryo,  heart,  309 
Embryology,  3 
Emulsions,  21 
Enchylema,  17 
Endo-enzymes,  34 
Endoplasm,  17 
Endosmometer,  141 
Energy,  kinetic  and  potential,  44 

conservation,  5 
Enterokinase,  30 
Enzymes,  blood,  127 

classification,  31 

properties,  29 
Erepsin,  32,  34 
Erythroblasts,  535 
Erythrocytes,  blood,  100,  146 

lymph,  513 
marrow,  535 

nucleated,  536 
Eudorina,  colony,  15 
Eupnoea,  403,  467 
Eustachian  valve,  182 


Evolution,  46 
Exchange,  gas,  375,  387 
Excitability,  44 

heart,  313 
Expiration,  419 
Expiratory  centres,  454 
Expired  air,  397 
Exploring  sound,  cardiac,  200 

sound,  oesophageal,  228,  406,  429 

sound,  rectal,  429 
Extraction,  gas,  377 
Extra-systole,  320 

Facial  nerve,  vaso-constriction,  348 
Fatigue,  73 
Fats,  cell,  35 

plasma,  130 

respiratory  quotient,  399 
Femoral  sphygmogram,  270 
Ferment,  fibrin,  128 
Ferments,  21,  39 
Ferric  album inate,  551 
Fibrin,  97 

ferment,  129,  137 
Fibrinogen,  125,  128 
Fibrinoglobuliu,  135 
Fibroin,  25 

Filtration,  lymph,  521 
Fistula,  lymphatic,  512 

pericardial,  215 
Foetus,  apnoea,  477 

lung,  405 
Follicles,  agminated,  530 

solitary,  529 

Formatio  reticularis,  445 
Frog,  heart,  286 

nerves  of  heart,  328 
Fructose,  36 

Fumaria  hygrometrica,  59 
Fungi,  57 
Funiculus  solitarius,  445 

Galium  aparina,  79 

Galvanotaxis,  80 

Ganglia,  heart,  299 

Ganglion,  Gasserian,  328,  354 

"Gas  silvestre,"  371 

Gases,  absorption  and  diffusion,  378 

atmospheric,  397 

blood,  379,  384,  388 

extraction,  382 

lymph,  514 

plasma,  132 

physics,  378 

protoplasm,  38 

respiratory,  387 
Gasometric  apparatus,  484 
Gelatin,  23 
Gelatose,  23 
Geomorphosis,  49 
Geotaxis,  77 
Giant  cells,  535 
Glands,  haemolymphatic,  557 


INDEX  OF  SUBJECTS 


565 


Glands,  lymphatic,  530 

submaxillary,  343 
Gliadins,  23 
Globulins,  23 

serum,  126,  128 
Globulose,  23 

Glosso  -  pharyngeal    nerve,    circulation, 
360 

respiration,  465 
Glottis,  respiration,  421 
Glucoproteins,  23,  25 
Glucosamine,  27 
Glucose,  36 

blood,  130 
Glutaminic  acid,  27 
Glutelins,  23 
Glycine,  27 
Glycogen,  18,  37 

blood,  130 

Glycolysis,  blood,  127 
Gly co proteins,  23 
Glycyl-glycine,  28 
Glycyl-tyrosine,  23 
Granules,  leucocytes,  114 

protoplasm,  17 
Gum,  animal,  130 
Gums.  37 

Haemacytometers,  102 
Haemapoiesis,  medullary,  534,  538 

splenic,  550 
Haematin,  108 
Haematoblasts,  118 
Haematocrite,  104,  148 
Haematoidin,  109 
Haematoporphyrin,  109 
Haemautograph,  265 
Haemin,  108 
Haemochromogen,  108 
Haemodiastase,  127 
Haemodromograph,  257 
Haemodromometers,  257 
Haemodynamics,  233 
Haemoglobin,  105,  107,  109 

carbon  dioxide,  386 

derivatives,  108 

oxygen,  383 

Haemoglobinometer,  121 
Haemoglobinuria,  153 
Haemolymphatic  glands,  557 
Haemolysis,  105,  143,  154 

splenic,  550 
Haemorrhage,  152 
Haemotachometer,  274 
Heart,  anatomy,  182 

apparatus,  287 

automatic  regulation,  210 

automatism,  298,  305 

block,  315 

cycle,  180 

delirium  of,  321 

embryo,  309 

frog,  286 


Heart,  ganglia,  299 

impulse,  221 

inhibition,  322 

inhibition,  reflex,  336 

intrathoracic  pressure,  436 

intrinsic  nerves,  299 

invertebrate,  311 

ligature,  Stannius,  299 

limulus,  311 

locomotion,  224 

mechanics,  180,  187,  190,  201 

myo-  and   neurogenic    theories,    307, 
308,  310 

nerves,  accelerator,  327 

nerves,  depressor,  333 

nerves,  inhibitory,  322 

oxygen,  293 

perfusion,  289 

phases  of  Luciani,  302 

plethysmograms,  216 

refractory  period,  320 

resuscitation,  298 

rhythmicity,  298,  322 

self- steering  action,  210 

sounds,  196,  198 

staircase,  318 

survival,  298 

tonicity,  319 

tortoise,  286 

urea,  297 

valves,  187,  190 

volume  changes,  215 

work,  230 
Hearts,  lymph,  516 
Heat,  death,  71 

stimulus,  77 
Heliotaxis,  78 

Hemiplegia,  respiratory,  444,  452 
Heredity,  49 
Heterogenesis,  52 
Hibernation,  respiration,  496 
High  altitudes,  blood,  384 
Hippuric  acid,  129 
Histidine,  27 

Histogenic  substances,  126 
Histolytic  substances,  93,  126 
Histones,  23,  24,  106,  117 
History,  circulation,  157 

respiration,  369,  402 
Hyaloplasm,  17 
Hydraemia,  143,  152 
Hydrobilirubin,  110 
Hydrodynamics,  circulation,  232 
Hydrogel,  21 
Hydrogenase,  34 
Hydrolysis,  26,  32 
Hydromorphosis,  49 
Hydi-osol,  21 
Hyperaemia,  active,  341 

paralytic,  345 
Hyperpnoea,  469 

Hypoglossal  nerve,  vasomotors,  348 
Hypoxanthine,  24,  35 


566 


PHYSIOLOGY 


Ichthulin,  2-3 
Ictus  cordis,  222 
Idioplasm,  50 
Immunity,  154 
Impulse,  heart,  221 
Inanition,  65 
Inflammation,  176 
Infundibula,  lung,  403 
Inhibitory  centres,  heart,  336 

centres,  respiration,  452 

nerves,  heart,  322 
Inorganic  constituents,  cell,  37 

constituents,  serum,  131 
Inotropism,  heart,  326,  330 
Inspiration,  409 
Inspiratory  centres,  454 

muscles,  409 

Intercartilaginous  muscles,  414 
Intercostal  muscles,  411 
Intermolecular  oxygen,  394 
Internal  respiration,  375 
Intersystole,  201 
Intra-abdomiiial  pressure,  427 
Intracardiac  pressure,  201 
Intrapleural  pressure,  428 
Intrapulmonary  pressure,  405,  424 
Intrathoracic  pressure,  406,  427,  436 
Inversion,  sugars,  37 
Invertase,  33 
Invertebrate  heart,  311 
Ions,  32 
lonisation,  142 
Iron,  haemoglobin,  108 

metabolism,  bacteria,  65 

spleen,  551 

Ischaemia,  active,  342 
Isoleucine,  27 
Isotony,  142 

Jecorin,  plasma,  130 

Kata-,  vide  Cata- 
Katabolism,  43 
Keratin,  25 
Kinase,  blood,  139 
Kinases,  30 
Kinetic  energy,  44 
Knephoplankton,  83 
Kymograph,  242 

Lactacidase,  34 

Lactase,  34 

Lacteals,  171 

Lactose,  37 

Laevulinic  acid,  24 

Laevulose,  37 

Lamarckism,  48 

Laryngeal  nerves,  respiration,  465 

Larynx,  respiration,  419,  421 

Latent  life,  65 

systole,  206 

Laughter,  mechanism,  438 
Laws  of  gases,  378 

of  solutions,  141 


Laws  of  variation,  48 
Lecithin,  35,  130 
Leech,  coagulation,  124 
Leucaemia,  116 
Leucine,  27 
Leucocytes,  blood,  113 

chemistry,  117 

chemotaxis,  116,  178 

coagulation,  138 

diapedesis,  115 

lymph,  513 

marrow,  534 

movement,  115 

narcosis,  178 

origin,  114 

phagocytosis,  115 
Leucocytosis,  152 
Leuconuclein,  138 
Leucyl-glutamic  acid,  23 
Levatores  costarum,  410 
Life,  minimal,  67 

physical  basis,  11 

potential,  65 

pressure,  71 

temperature,  70 
Light,  a  stimulus,  78,  81 
Limbs,  vasomotor  nerves,  349,  354 
Limulus,  heart,  311 
Lipase,  33 

blood,  127 
Locomotion,  arteries,  277 

heart,  224 
Lungs,  foetal,  405 

gas  exchange,  387 

movements,  426,  442 

structure,  403 

ventilation,  423,  484,  487 
Luxus  respiration,  473 
Lymph,  505 

blood-,  512 

cells,  513 

circulation,  515 

composition,  513 

nitration,  521 

formation,  519 

gas,  514 

hearts,  516 

injection  of,  533 

liver,  514 

post  mortem,  515 

quantity,  514 

secretion,  519 

sources,  512 

tissue-,  512 

transudation,  524 

velocity,  516 
Lymphagogues,  523 
Lymphatic,  canaliculi,  509 

cavities,  514 

fistula,  513 

pressure,  516 

stomata,  510 

system,  505 


INDEX  OF  SUBJECTS 


567 


Lymphatic  vessels,  506 
Lymphatics,  perivascular,  507 
Lymphocytes,  114,  513,  529 
Lymphoid  follicles,  529 

tissue,  528 
Lysine,  27 

Macrocytes,  101 
Maltase,  33 
Maltose,  33 
Manometer,  elastic,  244 

maximum  and  minimum,  207 

mercury,  244 
Marine  organisms,  81 
Marrow,  534 

cells,  535 

haemapoiesis,  538 

phagocytosis,  537 
Materialism,  5 
Matter,  conservation,  5 

inorganic,  organism,  37 

inorganic,  serum,  131 
Mechanical  stimuli,  76 
Mechanics,  heart,  180 

respiration,  402 
Mechanism,  protoplasmic,  85 
Mechanomorphosis,  49 
Medulla  oblongata,  blood-vessels,  361 

heart,  336 

respiration,  443 
Megacaryocytes,  535 
Meiocardia,  186,  215 
Melanins,  25 
Membrane,  cell,  13 

semi-permeable,  141 
Merotomy,  12 
Metabolism,  allonomous,  87 

autonomous,  86 

in  animals,  42,  61 

in  plants,  54 

in  saprophytes,  60 

of  mineral  matter,  62 

splenic,  552 

Metabolites,  protein,  35,  129 
Metaglobulin,  125 
Metaprotein,  23 
Metazoa,  11 
Methaemoglobin,  125 
Microcytes,  101 
Migratory  cells,  175 
Milk,  -clotting,  135 
Mimosa  pudica,  53 
Mineral  matter,  cell,  37 

matter,  metabolism,  62 

matter,  serum,  131 
Mitral  valve,  190 
Molecular  concentration,  141 
Monism,  6 
Monosaccharides,  36 
Morphology,  2 
Mosquitoes,  coagulation,  124 
Motor  nerves,  respiration,  441 
Mountain  sickness,  474 


Movements,  amoeboid,  16,  74,  115 

arterial,  277 

cardiopneiimatic,  227 

pulmonary,  426,  442 
Mucoid,  serum,  126 
Murmurs,  bronchial,  427 

cardiac,  198 

vesicular,  427 
Muscle,  bronchial,  442 

cardiac,  285 

respiration  of,  394 

sound  of,  197 

vascular,  427 
Muscles,  expiratory,  419 

inspiratory,  409 

of  neck,  410 

of  thorax,  412 
Muscular  dyspnoea,  471 
Mutation,  51 
Myocardium,  182,  312 

conductivity,  313 

excitability,  313 
Myogenic  theory,  heart,  307 
Myosin,  23 
Myosinogen,  23 
Myxomycetes,  protoplasm,  15 

Nagelism,  49 

Narcosis,  leucocytes,  178 

Nasal  mucosa,  respiration,  465 

Nasal  respiratory  movements,  422 

Neo-Darwinism,  47 

Neo-Lamarckism,  49 

Neo-vitalism,  5 

Nepenthes,  55 

Nerve  cells,  survival,  310 

Nerves,  afferent  cardiac,  333,  360 

afferent,  respiratory,  457 

bronchial,  442 

efferent  cardiac,  322,  327 

efferent  lymphatic,  517 

efferent,  respiratory,  441 

neck,  rabbit,  334 

respiratory  exchange,  392 

secretory,  522 

submaxillary  gland,  343,  522 

vasomotor,  341 
Nervi  erigentes,  355 
Neurogenic  theory,  heart,  310 
Nitrifying  bacteria,  57 
Nitrogen,  372 

blood,  377,  386 

expired  air,  397 
Nodulus  Arantii,  187 
"Nceud  vital,"  444 
Non-electrolytes,  142 
Nucleic  acid,  24 

acid,  coagulation,  138 
Nuclein,  23,  35,  49 
Nucleohistone,  138 
Nucleolus,  39 
Nucleoproteins,  23,  24 
Nucleus,  anterolateral,  363 


568 


PHYSIOLOGY 


Nucleus  cell,  13 

cell,  chemistry,  39 

cell,  structure,  19 
Nutrition,  64 

Occlusion  of  trachea,  460 

Octadecapeptide,  29 

Oedema,  520 

Oenothera,  52 

Oesophageal  sound,  429 

Olfactory  nerves,  respiration,  465 

Oligocythaemia,  152 

Ontogeny,  2,  46 

Optic  nerve,  respiration,  465 

Optical  activity,  protein,  21 

Organisms,  elementary,  11 

aerobic,  68 

anaerobic,  68 
Osazones,  37 
Osmotic  pressure,  blood,  142 

pressure,  fish,  145 

pressure,  lymph,  515 

pressure,  serum,  147 
Ovalbumin,  23 
Ovomucoid,  126 
Oxalates,  coagulation,  125 
Oxidases,  33 
Oxygen,  absorption,  lung,  389 

blood,  380 

discovery,  372 

expired  air,  389,  397 

haemoglobin,  383 

heart,  293 

intermolecular,  394 

life,  68 

nerve  centres,  394 
Oxy  haemoglobin,  106 

dissociation,  395 
Oxyproline,  27 
Oxypyrrolidine-carboxylic  acid,  27 

Palaeontology,  2 

Pancreas  of  Aselli,  533 

Panteplankton,  83 

Papain,  32,  54 

Paracasein,  136 

Paraglobulin,  126 

Paralysis,  73 

Paramoecium,  galvanotaxis,  80 

geotaxis,  77 
Parasites,  60 

Partial  pressure,  respiration,  389 
Patches  of  Peyer,  530 
Pause,  cardiac,  180 

respiratory,  499 
Pentoses,  24 
Pepsin,  32 
Peptones,  23 
Percussion,  lungs,  425 
Perfusion,  289 
Pericardium,  fistula,  209,  215 

pressure,  219 


Periodic  respiration,  492,  494 

Peripheral  stream,  189 

Perisystole,  180 

Perivascular  lymphatics,  507 

Pernicious  anaemia,  539 

Peroxidases,  33 

Phagocytes,  18,  115,  178,  537 

Phaoplankton,  83 

Phases,  heart,  Luciani's,  302 

Phenomena,  objective  and  subjective,  6 

psychical.  7 

vital,  1,  42 
Phenomenalism,  7 
Phenyl-alanine,  27 
Phenyl-glucosazone,  37 
Phenyl-hydrazine,  37 
Phlebograms,  204 
Phlogiston,  373 
Phlogosin,  178 
Phosphates,  cell,  48 
Phosphoproteins,  23,  24 
Phosphorus,  reaction,  39 
Photomorphosis,  49 
Phototaxis,  78 
Phrenic  nerves,  441 
Phrenograph,  416 
Phylogeny,  2,  46 
Physical  basis  of  life,  11 
Physiology,  scope,  3 
Piezometer,  233 
Pigments,  25 

"  Pince  cardiographique,"  289 
Pinocytosis,  534 
Pitot  tubes,  234 
Plankton,  82 
Plants  and  animals,  53,  55 

insectivorous,  53 
Plasma,  blood,  123,  142 

carbohydrates,  130 

electrical  conductivity,  144,  149 

fats,  130 

gas,  132 

histogenic  matter,  93,  126 

histolytic  matter,  93 

incoagulable,  124 

inorganic  matter,  131 

molecular  concentration,  141 

osmotic  pressure,  142 

proteins,  125,  126 

viscosity,  151 

lymph,  513 
Plasmodium,  113 
Plateau,  systolic,  206 
Platelets,  blood,  117 

blood,  coagulation,  134 
Plethora,  100 
Plethysmograms,  216,  279 
Plethysmographs,  278,  344 
Pleura!  cavity,  403,  425 
Pluralism,  7 
Pneumograph,  415 
Pneumoplethysmograph,  425 
Pneumothorax,  406 


INDEX  OF  SUBJECTS 


569 


Poikilocytes,  101 
Polycythaemia,  153 
Polypeptides,  23,  28 
Polypnoea,  470 
Polysaccharides,  37 
Post-mortem  lymph,  515 
Potential  energy,  68 
Pressure,  alveolar,  405,  424 

arterial,  241,  243,  253 

capillary,  253 

intra-abdominal,  427 

intracardiac,  201,  208 

'intrathoracic,  406,  427 

lymphatic,  513,  516 

osmotic,  141 

pericardial,  219 
Presystole,  180 
Pro-enzymes,  30 
Proline,  27 
Propeptones,  23 
Prosthetic  group,  protein,  24 
Protagon,  35 
Protamines,  23,  24 
Proteins,  20 

classification,  23 

cleavage,  26,  28 

coagulation,  21 

conjugated,  23,  24 

of  plasma,  125,  126 

properties,  21 

reactions,  21,  22 

respiratory  quotient,  399 

structure,  25 
Proteoses,  23 
Prothrombin,  137 
Protista,  13 
Protistology,  3 
Protoplasm,  17,  18 

myxomycetes,  15 
Protozoa,  11 
Pseudopodia,  16 
Ptyalin,  33 
Pulmonary  arterial  pressure,  254 

catheter,  388 

circulation,  discovery,  160 

epithelium,  absorption,  391 

gas  exchanges,  387 
Pulp,  splenic,  547 
Pulse,  arterial,  263 

cardiac,  221 

negative  cardiac,  227 

negative  pulmonary,  227 

negative  thoracic,  227 

negative  venous,  203,  227 

wave,  240,  271 
Purine,  24 
Pus,  115 
Pycnometer,  95 
Pyrimidine,  24 

Quantity  of  blood,  99 

of  lymph,  514 
Quotient,  respiratory,  398 


Radial  sphygmogram,  264 
Radiolaria,  14 
Reaction  of  blood,  94 

of  lymph,  513 
Reactions  of  carbohydrates,  36 

of  proteins,  21 
Receptaculum  Chyli,  517 
Rectal  sound,  429 

Red  blood  corpuscles,  vide  Erythrocytes 
Reductase,  34 

Reduction,  by  carbohydrates,  36 
Reflexes,  cardiac,  336 

respiratory,  464 

vascular,  357 

Refractory  period,  heart,  320 
i    Regeneration,  84 

blood,  152 
Reproduction,  43 
Reserve  air,  423 
I    Residual  air,  423 
Resistance  capacity,  150 
Respiration,  abdominal,  416 

adaptation,  469 

afferent  nerves,  457 

chemistry  and  physics,  369 

Cheyne-Stokes,  492 

efferent  nerves,  441 

external,  376 

internal,  375,  393 

luxus,  472,  473 

mechanics,  402,  433 

nerve  centres,  394 

nervous  control,  440 

periodic,  492 

rhythm,  437,  440 
Respiratory  centres,  443,  451,  452,  464 

centres,  expiratory,  454 

centres,  inhibitory,  452 

exchanges,  379,  392 

hemiplegia,  444 

movements,  416 

pause,  499 

pressures,  429 

quotient,  398 

quotient,  carbohydrates,  399 

quotient,  fats,  399 

quotient,  proteins,  399 
Revolution  of  heart,  180 
Rheotaxis,  76 
Rhizobium,  58 
Rhizopoda,  13 
Rhythm,  heart,  333 

respiration,  437,  440 

respiration,  automaticity,  461 

respiration,  control,  440 

respiration,  periodic,  492 
Rhythmicity,  heart,  298,  322 
Ribs,  408 

Saccharomyces  cerevisiae,  30,  60 
Saccharoses,  37 
Salmine,  23 
Salts,  37 


570 


PHYSIOLOGY 


Salts,  heart,  295 

Saprophytes,  57,  69 

Sarkine,  35 

Scalene  muscles,  410 

Schizomycetes,  57 

Sciatic  nerve,  vaso-constrictors,  351 

Sclero-proteins,  23,  25 

Scombrine,  24 

Scotoplankton,  83 

Secretion,  and  lymph  formation,  522 

of  lymph,  519 
Selection,  germinal,  50 

natural,  46 

Self-steering  action  of  heart,  210 
Semilunar  valves,  187 
Semipermeable  membranes,  141 
Sensations,  6,  45 
Sensibility,  45 
Sensitive  plants,  53 
Septum,  auricular,  299 
Serin,  126 
Serine,  27 
Sero-mucoid,  126 
Serous  cavities,  514 

effusions,  515 
Serum,  97,  127 

ash,  131 

carbohydrates,  130 

conductivity,  150 

enzymes,  127 

fats,  127 

measurement    of    osmotic    pressure, 
144,  147 

toxicity,  153 
Serum  albumin,  126,  128 

globulin,  126 
Silkworm,  70 
Sinus  of  Yalsalva,  187 

venosus,  286 
Skeleton,  thoracic,  407 
Sleep,  501 
Sneezing,  438 
Soaps,  plasma,  130 
Sobbing,  438 
Solutions,  colloid,  21 

laws  of,  141 

normal  physiological,  293 
Sound,  exploring,  cardiographic,  200 
,    exploring,     oesophageal,     228,     406, 
429 

exploring,  rectal,  429 

muscle,  197 
Sounds,  heart,  196 
Spaces,  lymphatic,  509 
Species,  46 

Spectrophotometer,  109 
Sphygmograms,  analysis,  271 
Sphygmographs,  264 
Sphygmomanometer,  245 
Sphygmoscope,  205 
Spinal  centres,  respiratory,  451 

centres,  splenic,  554 

centres,  vasomotor,  362,  364 


Spiritus  igneo-aereus,  372 

Spiritus  nitro-aereus,  372 

Spirograph,  425 

Spirometer,  422 

Spirostomum,  81 

Splanchnic  nerves,  blood-vessels,  348 

lymph  vessels,  518 

respiration,  465 
Spleen,  545 

cells,  549 

contractility,  553 

extirpation,  550 

haemapoiesis,  550 

haemolysis,  551 

lymphapoiesis,  552 

metabolism,  552 

nerves,  549 

nerve  centres,  554 
Spongin,  23,  25 
Staircase,  heart,  318 
Staphylococcus,  178 
Starch,  37 
Steapsin,  33 
Stentor,  14 

Sternum,  asthma,  410 
Stethograph,  415 
Stimuli,  73 

chemical,  73 

electrical,  80 

internal,  83 

luminous,  78 

mechanical,  76 

thermal,  77 
Stomata,  510 

Stromata,  erythrocytes,  106 
Stromuhr,  257 
Sturine,  23 

Submaxillary  gland,  343 
Substances,  histogenic   and  histolytic, 

93,  126 
Sugars,  36 
Sulphates,  38 

Sulpho-methaemoglobin,  110 
Sulphur,  protein,  22 
Sulphur  metabolism,  bacteria,  65 
Suppuration,  115,  178 
Surface  area,  capillaries,  263 

thoracic,  417 
Survival,  heart,  298 
nerve  centres,  310 
Suspension  of  artery,  245 

of  heart,  290 
Suspensions,  colloid,  21 
Swimming-bladder,  gas  of,  390 
Symbiosis,  58 
Sympathetic  nerve,  blood-vessels,  342 

nerve,  heart,  328 
Syncytium,  15 

System,  circulatory,  157,  180 
lymphatic,  505 
respiratory,  369 
vegetative  and  animal,  92 
Systole,  185 


INDEX  OF  SUBJECTS 


571 


Systole,  aspiration,  208 

latent,  206 
Systolic  plateau,  206 

Tachograms,  275 
Tachypnoea,  461,  470 
Tambour,  recording,  201 
Temperature,  and  life,  70 
Tension  of  gases,  alveolar  air,  390 

of  gases  in  atmosphere,  388 

of  gases  in  blood,  388,  389 

of  gases  in  expired  air,  389 
Tetanus,  electrical,  80 

mechanical,  76 

thermal,  77 
Thallassicolla,  14 
Thermal  dyspnoea,  470 

stimuli,  77 

Thermomorphosis,  49 
Thermotaxis,  78 
Thigmotaxis,  76 
Thoracic  duct,  171 

respiration,  416 
Thoracometer,  415 
Thorax,  skeleton,  407 

surface  area,  417 
Thrombin,  137 
Thrombokinase,  139 
Thrombosin,  135 
Thrombosis,  133 
Thymine,  24 
Thymus,  540 

extirpation,  542 

feeding,  545 

structure,  541 
Tidal  air,  422 
Tissue,  lymphoid,  528 
Tissues,  13 

and  lymph,  505 

respiration  of,  393 
Tone,  arterial,  262,  344,  346 
Tonicity,  heart,  319 
Tonograph,  heart,  288 
Tonometer,  arterial,  244,  252 
Tortoise,  heart,  286 
Trachea,  403 
Tradescantia,  18 
Transfusion,  blood,  152 
Transplantations,  13 
Transudation,  lymph,  524 
Tricuspid  valve,  191 
Trypsin,  32 
Tryptophane,  27 
Tubes,  bronchial,  403 

elastic,  239 

Types  of  respiration,  416 
Tyrosine,  27 

Ultramicroscope,  21 
Uracil,  24 
Urea,  33,  35 

heart,  297 

plasma,  129 


Urease,  33 

Uric  acid,  129,  552 

Urobilin,  109 

Vacuoles,  cell,  18 
Vago-sympathetic  trunk,  328,  353 
Vagus,  apnoea,  479,  488 

cardiac,  218 

cardiac,  anabolic  action,  332 

cardiac,  bathmotropic  effect,  327 

cardiac,  chronotropic  effect,  325 

cardiac,  dromotropic  effect,  326 

cardiac,  inotropic  effect,  326 

laryngeal,464 

pulmonary,  afferent  fibres,  462 

pulmonary,  efferent  fibres,  442 

pulmonary,  section  of,  462 
Valve,  Eustachian,  182 
Valves,    cardiac,    auriculo-  ventricular, 
192 

cardiac,  semilunar,  187 

veins,  165 

Variability  of  species,  45,  47 
Variation,  47 

and  Quetelet's  law,  48 
Vaso-constrictor  centres,  361 

nerves,  347 
Vaso-dilatator  centres,  365 

nerves,  350 
Vasomotor  centres,  361 

nerves,  341 

nerves,  ear,  343 

nerves,  head  and  neck,  34S 

nerves,  limbs,  349,  354 

reflexes,  357 

viscera,  348 
Veins,  pressure  in,  253 

pulsation,  203 

valves  of,  165 

velocity  in,  262 
Velocity,  blood,  174,  263 

in  arteries,  256,  261 

in  capillaries,  263 

of  lymph  formation,  523 

in  veins,  262 

of  lymph,  516 
Vena  arteriosa,  159 
Venosity  of  blood,  dyspnoea,  469 
Venous  pressure,  253 

pulse,  203 

valves,  165 

Ventilation,  lungs,  423,  484,  487 
Ventricles,  pressure  in,  201 

structure,  183 

systole  and  diastole,  185 
Vessels,  blood,  341 

lacteal,  171 

lymphatic,  506 
Vicia  fabia,  58 
Viscosimeter,  151 
Viscosity,  blood,  151 
Vital  capacity,  423 
Vitalism,  5 


572 

Vitellin,  23 
Volume,  heart,  215 
Voluntary  apnoea,  480 
Vortices,  arterial,  189 

Water,  life,  66 
Wave,  pulse,  240 

dicrotic,  269 

velocity,  273 
Work,  heart,  230 


PHYSIOLOGY 


Xanthine,  24,  130,  298,  552 
Xanthoproteic  test,  22 

Yawning,  438 

Zea  mais,  59 
Zoospores,  16 
Zymase,  30 

blood,  127 
Zymogens,  30 


INDEX    OF    AUTHORS 


ABDERHALDEN,  amino-acids,  26 

physiological  chemistry,  39 

proteins,  26 

ABELOUS,  thymus,  543,  557 
ADAM,  automatism  of  heart,  306 

resuscitation  of  heart,  298 
ADAMI,  accelerator  nerves,  329 

systole,  182 
ADAMKIEWICS,   intrathoracic   pressure, 

427 

ADAMS,  G.  P.,  phototropism,  90 
ADAMUK,  vasomotor  centres,  365 
ADDISON,  "W.,  coagulation  of  blood,  133 

diapedesis,  175 
ADUCCO,  active  expiration,  420,  439 

bulbar  centres,  448,  449,  489,  504 

physiology,  text-book,  9 

respiratory  centres,  454 
ALBANESE,  oxygen  and  heart,  293 

viscosity  of  blood,  151 
ALBERTONI,  accelerator  nerves,  329 

cocaine  and  protoplasm,  102 

peptone  blood,  124 

transfusion,  153" 

ALBINI,  diastolic  aspiration,  211 
ALBRECHT,  active  diastole,  214 
ARANTIUS,  intercostal  muscles,  411 

nodule  of,  187 

ARISTOTLE,  respiration,  369,  380 
ARLOING,  heart,  231 

vagus,  324 

ARNOLD,  lymphatic  organs,  557 
ARON,  intrathoracic  pressure,  427 
ARRHENIUS,  electric  conductivity,  149 

ionisation,  142 

solutions,  142 

ARRONET,  plasma  and  corpuscles,  125 
ARRONS,  isolation  of  heart,  291 
D'ARSONVAL,  expired  air,  397 
ARTHUS,  coagulation  of  blood,  136 

lipase  of  blood,  127 
ASELLI,  pancreas  of,  533 

lymphatic  system,  171,  505 
ASHER,  formation  of  lymph,  526,  558 

injection  of  lymph,  533 

innervation  of  blood-vessels,  367 

post-mortem  lymph,  515 


|    ASHER,  tissue  lymph,  527    557 
ASP,  cardiac  reflexes,  336 

splanchnics,  348 
AUBERT,  cardiac  vagus,  336 

BACCELLI,  heart-beat,  222 

spleen,  553 
BACHMAN,  conditions  of  cardiac  activity, 

298,  338 
BAGLIONI,  apnoea,  491 

nerve  centres  and  oxygen,  394 

respiratory  reflexes,  466,  504 

urea  and  heart,  297,  338 
BAHR,  heart-beat,  225 
BAIN,  spleen,  551,  558 
BAINBRIDGE,  post-mortem  lymph,  515, 

558 
BALDWIN,    T.    INI.,    development    and 

evolution,  63 
BALE  AN,  H.,  blood,  122 
BAMBERGER,  heart- beat,  225 
BANCROFT,  J.  AV.,  galvanotaxis,  90 
BARBERA,  injection  of  lymph,  533,  557 

tissue  lymph,  527,  557 
BARCROFT,  J.,  blood  gases,  401 

blood,  urea,  156 

metabolism,  400,  401 
BARRAL,  glycolysis  in  blood,  127 
BARRY,  mechanics   of    thoracic   move- 
ments, 429 
BARTHOLIN,  circulation,  166 

formation  of  lymph,  519 

intercostal  muscles,  411 

lymphatic  system,  172,  505 
BARTLETT,  J.  H.,  blood  pressure,  439 
BASCH,  thymus,  545 
v.  BASCH,  plethysmograph,  344 

sphygmomanometer,  245 
BATESON,  evolution,  62,  63 
BAUMANN,  E.  P.,  haemorrhage,  156 
BAUMGARTEN,        auriculo  -  ventricular 

valves,  192 
BAXT,  accelerator  nerves,  330 

cardiac  nerves,  331,  338 
BAYLE,  respiration,  412 
BAYLISS,  W.  M.,  acceleration  of  heart, 
330 


573 


574 


PHYSIOLOGY 


BAYLISS,  W.  M.,  cardiac  vagus,  326 
caseinogen,  40 

intracardiac  pressure,  201,  207 
systole,  206 
vascular  tone,  346,  368 
vaso-constrictors  of  limbs,  349 
vaso-dilatators  of  limbs,  354,  367 
vasomotor  reflexes,  368 
BE  ALE,  coagulation  of  blood,  133 
BEAU,  heart-beat,  222 

intercostal  muscles,  411,  439 
thoracic  respiration,  417 
BEAUNIS,  physiology,  text-book,  9 
BECCARI,  venous  pulse,  203 
BECHT,  F.  C.,  salivary  glands,  558 
BECHTEREW,  vasomotor  centres,  366 
BECKMANN,  cryoscopy,  148 
BEHRING,    bacteriolytic     functions     of 

blood,  154 

BELFIELD,  vascular  reflexes,  360 
BELL,  law  of,  354 
v.  BENEDEX,  centrosome,  13 
BENEDIKT,  S.  K,  heart,  339 
BERAUD,  active  diastole,  213 
auriculo-ventricular  valves,  192 
elasticity  of  blood-vessels,  239 
BERGENDALL,       intercartilaginous 

muscles,  415 
BERGMANN,  intercartilaginous  muscles, 

415 

respiration,  373,  400 
BERKELEY,  phenomenalism,  7 
BERKLEY,  myocardium,  314 
BERKOWITSCH,  vasomotor  centres,  363 
BERNARD,  anaesthetics  on  animals  and 

plants,  53 
blood  pressure,  253 
cardiac  reflexes,  336 
cardiac  vagus,  323 
cervical  sympathetic,  341,  348 
chorda  tympani,  341,  350,  367 
facial  nerve,  348 
general  physiology,  89 
haemodiastase,  137 
sensibility  and  excitability,  45 
tissue  respiration,  394 
vaso-constrictors  of  limbs,  349,  367 
vasomotor  centres,  362,  367 
'  vasomotor  reflexes,  356 
BERNS,  apnoea,  485 
BERNSTEIN,  cardiac  centres,  337 
foetal  lungs,  405 
spirograph,  425,  439 
vascular  tone,  346 
vasomotor  nerves,  352 
BERT,  atmospheric  pressure,  72 
bronchial  muscles,  442 
negative  pulse,  227 
oxygen  of  blood,  384,  400 
plants  and  oxygen,  56 
rectal  explorer,  429 
respiratory  tracings,  424 
thoracograph,  415 


BERT,  tissue  respiration,  393 
BERTOLUS,    velocity   of  blood    stream, 

275 

BERZELIUS,  blood,  94 
BETHE,  neurogenic  theory,  310 
BEUTNER,  intracardiac  pressure,  208 
BEVER,  accelerators  of  heart,  327 

splanchnic  nerve,  347,  367 
BEYER,  H.  G.,  vasomotor  centre,  367 
BEYERINCK,  nitrifying  bacteria,  58 
v.  BEZOLD,  accelerators  of  heart,  327 
cardiac  vagus,  324,  336,  337 
splanchnic  nerve,  347,  367 
vascular  reflexes,  359,  367 
vasomotor  centres,  362,  367 
Avater  content  of  organism,  38 
BIAL,  haemodiastase,  127 
BICHAT,  animal  and  vegetable  life,  91 
cardiac  ganglia,  299 
cardiac  diastole,  208 
lymph,  509 
BIDDER,  cardiac  ganglia,  299,  305 

cardiac  vagus,  333 

BIEDERMANN,  invertebrate  heart,  311 
BIELETZKY,  experimental  a.pnoea,  484 
BILLARD,  thymus,  543,  557 
BIOT,  periodic  respiration,  502 
BISCHOFF,  quantity  of  the  blood,  99 

respiration,  377 
BIZZOZERO,  blood-platelets,  118 
coagulation  of  blood,  134 
giant-cells,  535 
haemorrhage,  152,  539 
lymphatic  canaliculi,  511 
marrow,  534,  557 
serous  cavities,  511 
spleen,  550,  552 
BLACK,  respiration,  373,  400 
BLACKMAN,  J.    K.,  auricular  rhythm, 

339 

BOCHEFONTAINE,  vasomotor  centres,  365 
BOCKER,  respiratory  centres,  453 
BOERHAAVE,  intercostal  muscles,  411 
BOHM,  accelerators  of  heart,  329 
lymph  follicle,  532 
marrow,  536 
solitary  follicles,  529 
thymus,  541 

BOHR,  blood  gases,  383,  386,  390,  400 
carbon  dioxide  and  haemoglobin,  386 
oxyhaemoglobin,  395,  396 
BORDET,  chemotaxis,  leucocytes,  75, 178 
BORDONI,  experimental  apnoea,  484 
periodic  respiration,  494,  502,  504 
BORELLI,  intercostal  muscles,  403,  411 

respiration,  439 

BORUTTAU,    nervous  mechanism  of  re- 
spiration, 504 
BOTAZZI,    embryonic    heart,    309,    321, 

337 
osmotic  pressure  of  blood,  144,  145, 

155 
physiological  chemistry,  39 


INDEX  OF  AUTHOKS 


575 


BOTAZZI,  tonicity  of  heart,  319 

viscosity  of  blood,  151,  155 
BOTKIN,  spleen,  553 
BOTSCHETSCHKAROFF,  spleen,  555 
BOTTGER,  test  for  sugar,  36 
BOURDON,  manometer,  277 
BOUSSINGAULT,  animals  and  plants,  55 
BOVERI,  centrosome,  13 
BOWDITCH,  cardiac  accelerators,  329 

preparation  of,  295,  303,  317,  337 

staircase  phenomenon,  318 

vasomotor  nerves,  352 
B&YCOTT,  A.  E.,  respiration,  439 
BOYLE,  law  of,  378 

respiration,  371,  378,  400 
BRACKET,  active  diastole,  213 
BRADFORD,  vascular  reflexes,  357 

vaso-constrictors  of  limbs,  349 

vaso-dilatators  of  viscera,  355 
BRANDE,  gas  extraction,  377 
BRANTLECHT,  proteins,  40 
v.  BRASOL,  formation  of  lymph,  525 
BRAUER,  centrosome,  13 
BREDIG,  catalysators,  31,  40 
BREFELD,  heat,  B.  Anthracis,  71 
BREUER,  respiratory  rhythm,  459 

inspiratory  centres,  456,  503 
BRODIE,  T.  G.,  bronchial  muscle,  504 

heart,  338 

metabolism,  401 

perfusion.  339 

pulmonary  vasomotors,  368 

serum  injections,  156 
BROWN,  bronchial  nerves,  442 

blood  pressure,  245 
BROWN,  A.  E.,    specific  characters,  63 
BROWN,  0.  H.,  blood  pressure,  284 
BROWN-S^QUARD,  cardiac   vagus,    323, 
333 

cervical  sympathetic,  342,  367 

experimental  apnoea,  476 

respiratory  centres,  444,  452,  504 

toxicity  of  expired  air,  397 

vascular  reflexes,  357 

vasomotor  centres,  364 
BRUCKE,  blood  plasma,  123 

coagulation  of  blood,  133 

elementary  organisms,  8 

heart,  self-steering,  210 

intercostal  muscles,  412 

lymphatic  glands,  533,  557 

semilunar  valves,  187 

spleen,  553 
BRUGH  VAN  DEII,  intrathoracic  pressure, 

427 

BUCHANAN,  coagulation  of  blood,  134 
BUCHNER,  ferments,  30 

tissue  respiration,  393 

zymase,  34 

BUCHNER,  H.,  alexines,  154 
BUDGE,  cardiac  nerve  centres,  336 

cardiac  vagus,  322,  335,  337 

cervical  sympathetic,  348 


BUDGE,  neurogenic  theory,  307 

vasomotor  centres,  365 
BUDGETT,  galvanotaxis.  80 
BUFALINI,  heart,  accelerators,  329 
BUFFON,  animals  and  plants,  1 
BUGARSKY,    serum,    osmotic    pressure, 

144 
BUGLIA,    non-coagulable    plasma,    124, 

155 
BUISSON,  arterial  pulse,  265 

negative  pulse,  227 

plethysmograph,  278 
BULGAK,  spleen  centres,  554 
BUNGE,  blood  plasma,  separation,  125 

plasma  ash,  131 
BUNSEN,  absorption  of  gas,  378 

partial  pressure,  379 
BURCKHARDT,  plasma,  126 
BURDACH,  heart-beat,  222 

intercostal  muscles,  411 
BURDON-SANDERSON,  cardiograph,  267 

sphygmograph,  267 

stethograph.  415 

BURKART,  expiratory  rhythm,  486 
BuRTON-C-PiTZ,  R.,  blood,  viscosity,  156 

venous  flow,  284 

venous  pressure,  284 
BUTSCHLI,  cell,  bacteria,  13 

cell,  structure,  17,  19 

CABMAN,  A.   W.,  cardiac  nerve  fibres, 
338 

respiratory  nerve  fibres,  338 
CAMIS,    J..    blood,    dissociation    curve, 

401 

CAMUS,  lymphatic  vessels,  517,  557 
CALORI,  venous  valves,  165 
CANNANUS,  venous  valves,  165 
CARBONE,  coagulation  of  blood,  155 

fibrin  ferment,  128 
CARDARELLI,  cardiac  vagus,  323 
CARLILE,  heart-beat,  224 

cardiac  systole,  186 
CARLSON,  A.  J.,  haemolytic  lymph,  559 

heart,  inhibition,  339 

heart,  invertebrate,  339,  340 

heart,  refractory  period,  339 

lymph  formation,  526,  559 

neurogenic  theory,  311,  337 

salivary  glands,  558 

vasomotor  nerves,  354,  368 
CARNOY,  structure  of  protoplasm,  17 
CARPENTER,  active  diastole,  214 
CARSWELL,  heart-sounds,  196 
CASPARI,  acapnia,  475,  504 
CASTELL,  oxygen  and  heart,  293 
CAVANI,  vascular  reflexes,  358,  367 
CAVAZZANI,  E.,  haemodiastase,  127 

red  blood-corpuscles,  101 
CAVENDISH,  composition  of  water,  374 
CECCHINI,  splenectomy,  557 
CERADINI,  auxocardia  and  meiocardia, 
186,  227 


576 


PHYSIOLOGY 


CERADINI,  circulation  of  blood,  161,  179 

diastolio  aspiration,  212 

heart,  self-steering,  211 

semilunar  valves,  187,  231 
CERVESATO,  thynms,  545 
CESALPINUS,  circulation,  163 

respiration,  371 
CESARIS  DEMEL,  red  blood-corpuscles, 

ioi 

CHAHCOT,  vasomotor  centres,  365 
CHAUVEAU,  auriculo-ventricular  valves, 
193 

cardiac  sound,  201 

haemodromograph,  211,  274 

heart,  231 

heart-beat,  225 

iiitersy stole,  196,  201 

intracardiac  pressure,  201,  206 

sphygmoscope,  244 

systolic  aspiration,  210 

velocity  of  blood  stream,  274 
CHELIUS,  plethysmograph,  278 
CHEVHEUL,  blood,  94 
CHEYNE,  periodic  respiration,  492 
CHORIOL,  active  diastole,  213 
CHRISTIANI,  cerebral  respiratory  centres, 

453 

CHUN,  Valdivia  expedition,  81 
CIAMICIAN,  sero-mucoids,  126 
CIGNA,  respiration,  373 
CLARKE,  antero-lateral  nucleus,  363 
CLARKE,    T.    W.,    sulph- haemoglobin, 

122 
COATS,  diastole,  209, 

cardiac  vagus,  325,  338 
COHNHEIM,  J.,  diapedesis,  115.  175 

leucocytes,  115 

lymph  formation,  524 

splanchnic  nerve,  348 
COHNHEIM,  0.,  erepsin,  32,  34 
COHNSTEIN,  lymph  formation,  524,  557 
COLASANTI,  dyspnoea,  470 

lactic  acid  in  urine,  470 
COLE,  proteins,  40 
COLIN,  intracardiac  pressure,  208 
COLOMBO,  blood  pressure,  248,  256 
COLUMBUS,  REALDUS,  circulation,  160 
CONCATO,  cardiac  vagus,  323 
CONKLIN,  E.  S.,  mutation,  63 
CONNSTEIN,  fats  and  blood,  127 
CONSIGLIO,  depressor  nerve,  335 

vascular  reflexes,  356 
COOPER,  capillary  circulation,  172 
CORRIGAN,  heart-beat,  222 
COSSY,  vaso-dilatators,  354 
CRAMER,  W.,  protagon,  40 
CRAMPTON,  H.  E.,  adaptation,  63 
CREDE,  splenectomy,  555 
CUBONI,  evolution,  52 
CUFFER,  periodic  respiration,  494 
CULLIS,  W.  C.,  perfusion,  339 
CUSANO,  arterial  pulse,  264 
CUSHNY,  A.  R.,  heart  rhythm,  231 


CUVIER,  animals  and  plants,  53 

.intercostal  muscles,  411 
CYON,  accelerator  nerves,  327,  337 

cardiac  nerves,  337 

depressor  nerves,  333,  360 

splanchnic  nerves,  347 

vaso-constrictor  nerves,  349 

vasomotor  centres,  366 
CZERMACK,  cardiac  vagus,  224 
CZERNY,  splenectomy,  555 

DAKIN,  H.  D.,  oxidation  of  ammo-acids, 
40 

oxidation  of  fat,  41 

DALAND,  molecular  concentration,  148 
DALE,  H.  H.,  galvanotaxis,  90 
DALLY,  J.  F.  H.,  diaphragm,  439 
DALTON,  diffusion  of  gases,  378 
DANILEWSKY,  injection  of  marrow  and 
spleen,  539,  558 

vasomotor  nerves,  365 
DARBISHIRE,  A.  D.,  heredity,  63 
DARCY,  hydrodynamics,  189 
DARWIN,  doctrine  of  descent,  46,  62 

insectivorous  plants,  53 
DASTRE,  coagulation  of  blood,  137 

cervical  sympathetic,  349,  353,  367 

extra-systole,  321 


splenectomy,  555,  558 
vascular  rettexc 


iexes,  361 

vasomotor  nerves,  353,  366 
DAVENPORT,  C.  D.,  evolution,  63 
v.  DAVIDOFF,  marrow,  536 

thymus,  541 

DAVIS,  B.  F.,  lymph,  559 
DAVY,  H.,  extraction  of  gas,  177 

residual  air,  423 
DAVY,  J.,  blood  gases,  377 
DAWSON,  P.  M.,  blood  pressure,  284 
DEAHNA,  vasomotor  centres,  366 
DEITERS,  formatio  reticularis,  446 
DELAGE,  Y.,  evolution,  62 
DELEZENNE,  anti-kinase,  128 

coagulation  of  blood,  139 
DENCKE,  resuscitation  of  heart,  298 
DENYS,  lymphatic  organs,  557 
DETTO,  evolution,  62 
DEW-SMITH,  heart  of  invertebrates,  311 
DIEMERBROCK,  intercostal  muscles,  411 
DINEUR,  galvanotaxis,  81 
DITTMAR,  vasomotor  centres,  363,  364 
DIXON,  W.  E.,  bronchial  muscle,  504 

heart,  401 

pulmonary  vasomotors,  368 
DOGIEL,  heart-sounds,  197 

serous  cavities,  509 

vascular  reflexes,  360 

velocity  of  blood  stream,  260 
DONDERS,  acceleration  of  heart  rhythm, 
181 

auriculo-ventricular  groove,  314 

cardiac  vagus,  324 

diastolic  aspiration,  211 


INDEX  OF  AUTHOKS 


DONDERS,  expiration,  419 

intrapulmonary  pressure,  405 

human  physiology,  231 

lungs  during  respiration,  425 

mechanics  of  thoracic  movements,  424, 
436 

surface  of  thorax,  417 

waves,  241 

DOUGLAS,  circulation  of  blood,  160 
DOUGLAS,  C.  G.,  Cheyne-Stokes  breath- 
ing, 504 

quantity  of  blood,  122 

regulation  of  respiration,  504 
DOYON,  accelerators  of  heart,  327 

lipase  of  blood,  127 

nerves  of  neck,  rabbit,  334 
DRECHSFELD,  cardiac  vagus,  336 
DROSDOFF,  spleen,  555 
DRUMMOND,    haemolymphatic    glands, 

557 

Du  BOIS-REYMOND,  E.,  dualism,  6 
Du    BOIS-REYMOND,     R.,    intercartil- 
aginous  muscles,  414 

mechanics  of  respiration,  439 

respiratory  movements,  466 
DUCCHESCHI,    blood    osmotic   pressure, 
144,  145 

blood  plasma,  127 

muscular  tone,  319 

sphygmography,  284 
DUCHENXE,  diaphragm,  410,  439 

intercostal  muscles,  411 

scalene  muscles,  410 
DUCLAUX,  anaerobic  organisms,  69 
DUKE,  W.  W.,  heart,  339 
DUMAS,  animals  and  plants,  55 

blood,  94 

DUNCAN,  diffusion  of  gases,  379 
DURANTE,  thrombosis,  133 
DUTROCHET,  endosmometer,  141 

v.  EBNER,  intercostal  muscles,  412 

intercostal  spaces,  409 
EBSTEIN,  E.,  diastole,  231 
ECKER,  spleen,  549 

ECKHARD,  automaticity  of  heart,  305, 
311 

cardiac  vagus,  324,  327 

heart  of  invertebrates,  311 

nervi  erigentes,  350,  355,  367 

neurogenic  theory,  307,  337 

vascular  reflexes,  359 

vasomotor  centres,  365 
EDELBERG,  coagulation  of  blood,  138 
EDGREN,  cardiograms,  224,  231,  268 

heart-sounds,  197 

latent  systole,  206 

sphygmograph    and    sphygmograms, 
267 

velocity  of  pulse  wave,  273 
EDWARDS,  W.,  respiration,  376,  400 
EECKE  (ver),  thymus,  544 
EGGERS,  H.  E.,  sinus  venosus,  339 

VOL.  I 


EGLI-SINCLAIR,     periodic     respiration. 

493 
EHRENBERG,  infusoria  and  temperature 

71 
EHRLICH,  anaerobic  organisms,  69 

examination  of  blood,  120 

leucocytes,  114 

red  blood -corpuscles,  100 
EICHHORST,  cardiac  vagus,  354 
EINBRODT,  mechanics  of  respiration  and 

circulation,  433 
EINTHOVEX,      intrathoracic      pressure,. 

427 

ELLINGER,  lymph  formation,  526,  558 
EMELIAXOW,  splenectomy,  556,  558 
EMMINGHAUS,  lymph  formation,  520 
ENGEL,  blood,  121 

blood-platelets,  119 

leucocytes,  114 
ENGELMANN,  active  vasodilatation,  347 

auriculo-ventricular  bundle,  314 

bacterium  photometricum,  78 

cardiac  nerves,  325,  331 

cardiogram,  290 

chemotaxis,  74 

compensatory  pause,  321 

electrical  stimuli,  80 

heart,  suspension,  290 

myogenic  theory,  308,  314,  337 

oxygen  and  ciliary  movement,  68 
ENGSTROM,  foetal  apnoea,  478 
VAN  ENSCHUT,  blood  gases,  377 
ERASISTRATUS,  arterial  pulse,  264 

circulation  of  blood,  159 

diastole,  208 

lacteals,  171 

respiration,  370 
ERB,  marrow,  539 
ERLANGER,  J.,  auricular  rhythm,  339 

auriculo-ventricular  bundle,  315 

heart-block,  339 

heart,  conduction,  340 
D'ERRICO,  lymphagogues,  523 

post-mortem  lymph,  515 
EULENBURG,  vasomotor  centres,  365 
EULER,  enzymes  and  catalysators,  32 
EUSTACHIUS,  lymphatic  system,  171 

valve  of,  182 
EWALD,  experimental  apnoea,  481,  504 

intrathoracic  pressure,  427 
EYKMAN,  molecular  concentration,  148 
EYSTER,  J.  A.  E.,  extra-systole,  339 

FABRICIUS,  valves  of  veins,  165 
FAIVRE,  blood  pressure,  253 

heart  beat,  225 
FANO,  active  movements  of  lungs,  442 

coagulation  of  blood,  134,  140 

embryonic  heart,  309 

histogenic  substances  of  plasma,  127 

metabolism  of  heart,  332 

myogenic  theory,  308,  337 

oscillations  of  auricular  tonicity,  319' 

2P 


578 


PHYSIOLOGY 


FANO,  osmotic  pressure  of  blood,.  144,    i 
155 

oxygen  and  heart,  293 

peptone  blood,  124 

periodic  respiration,  493,  497,  ;">04 

platelets,  118 

sp.  gr.  of  blood,  95 

tissue  respiration,  395 

tonicity  of  heart,  319 

vascular  reflexes,  357 
FANTINO,  cardiac  vagus,  333 
FARKAS,  reaction  of  blood,  94 
FASOLA,  active  movements  of  lungs,  442 
FEDERICO,  urea  and  heart,  297 
FERNET,  gases  of  blood,  383,  385 
FICK,  A.,  diaphragm,  417,  439 

diastole,  209,  213 

expiration,  419 

heart  beat,  313 

intercostal  muscles,  412 

intracardiac  pressure,  201 

manometer,  244 

medical  physics,  283 

plethysmograph,  278,  281 

pulse,  284 

thoracograph,  415 

work  of  heart,  230 

FICK,  R.,  respiratory  muscles,  415,  439 
FILEHNE,  periodic  respiration,  494,  498 
FILHOS,  active  diastole,  213 
FISCHER,  E.,  enzymes,  31 

phenyl-glucosazone,  37 

poly-peptides,  28,  39 

proteins,  26,  39 
FITZGERALD,    M.    P.,    alveolar    carbon   i 

dioxide,  439 
FLACK,  M.,  respiration  and  circulation,    , 

439 
FLEMMING,  examination  of  blood,  120 

lymph  follicle,  529 
FLETCHER,  W.  M.,  oxygen  and  muscle, 

90,  401 
FLOURENS,  circulation,  162 

noeud  vital,  444 

periodic  respiration,  494,  503 
FLUGGE,  bactericidal  properties  of  blood, 

154 
FOA,  marrow,  539 

megacaryocytes,  538,  557 

platelets,  119,  121 

spleen,  557 
FODOR,  bactericidal  properties  of  blood, 

154 
FONTANA,  extraction  of  gas,  377 

gas  of  blood,  377 

sleep,  502 

FORMANEK,  expired  air,  397 
FOSTER,  M.,  active  vasodilatation,  347 

cardiac  nerves,  328 

circulation  of  blood,  163,  179 

invertebrate  heart,  311 

lymphatic  circulation,  517 

phrenograph,  416 


FOSTER,  M.,  tissue  respiration,  395 
FOWLER,  marrow,  539 

spleen,  550,  556,  558 
FRAOASSATI,  respiration,  372,  400 

thoracic  duct,  171 

FRANCHINI,  inhibitory  centres  in  bulb, 
452 

pulmonary  vagus,  463 
FRANCK,  nitrifying  bacteria,  58 
FRANC.OIS-FRANCK,  accelerators  of  heart, 
330 

cardiac  plethysmograph,  289 

cardiac  reflexes,  336 

cardiac    vagus,    218,    326,    329,    335, 
338 

cardiograms,  223 

centres  of  cardiac  nerves,  336 

heart,  suspension,  291 

pericardial  fistula,  215 

plethysmograph,  278 

respiratory  centres,  453 

vascular  reflexes,  357 

vasomotor  centres,  365 
FRANK,  R.  T.,  conductivity  of  blood, 

156 

FRANKEL,  gas  of  blood,  384,  400,  474 
FRANZEL,  periodic  respiration,  502 
FRASSINETO,  DI,  plasma,  127 
FREDEUICQ,  aero  tonometer,  388 

apnoea  vera,  476,  504 

circulation  of  blood,  281 

experimental  apnoea,  476,  490 

gases  of  blood,  386,  390 

heart  beat,  231 

intracardiac  pressure,  203,  210 

latent  systole,  210 

oesophageal  sphygmograms,  229 

spleen,  553 

stimulation  of  pulmonary  vagus,  462 

systolic  aspiration,  203,  '210 

venous  pulse,  203 
FRERICHS,  urea  in  selachii,  297 
FREUND,  animal  gum,  130 

thrombosis,  133 
v.  FREY,  diastole,  209 

haematoidin,  108 

intracardiac  pressure,  201 

tonograph,  245 

vasomotor  nerves,  351 
FRIEDLEBEN,  thymus,  542 
FRIEDREICH,  auriculo-  ventricular  valves, 

192 

FROMMAN,  structure  of  protoplasm,  17 
FRY,  H.  J.  B.,  heart,  cephalopod,  340 
FUNKE,  haemoglobin,  107 

leucocytes,  175 

mechanics  of  respiration  and  circula- 
tion, 434 

spleen,  549 
FUSARI,  nerves  in  spleen,  549 

GABRITSCHEWSKI,  pinocytosis,  534 
GAD,  circulation  of  blood,  281 


INDEX  OF  AUTHOKS 


579 


GAD,  elimination  of  C02,  470 

experimental  apnoea,  477 

manometer,  245 

platelets,  119 

pulmonary  vagus,  458,  462 

residual  air,  423 

respiratory  centre,  446,  504 

respiratory  rhythm,  blood,  479,  486 

tachypnoea,  471 

GAGLIO,  lactic  acid  of  blood,  131 
GALEN,  active  diastole,  208,  213 

arterial  pulse,  264 

automatism  of  heart,  299 

circulation  of  blood,  159,  171 

"de  usu  partium,"  4,  9,  400 

intercostal  muscles,  411 

mechanics  of  respiration,  403 

pulmonary  vagus,  457 

respiration,  370 

respiratory  centres,  444 

semilunar  valves,  187 

spleen,  555 

systole  and  diastole,  180,  208 
GALEOTTI,    electrical    conductivity    of 
serum,  150 

electrical  conductivity  of  tissues,  155 
GAMGEE,  blood,  121 

oxyhaemoglobin  in  magnetic  field,  121 
GARDELLA,  coagulation,  124,  155 
GARELLI,  molecular  weights,  155 
GARTNER,    molecular    concentration   of 
blood,  148 

tonometer,   252 
GASKELL,  accelerator  nerves,  328 

active  vasodilatation,  347,  367 

auriculo-ventricular  bundle,  314,  316, 
321 

automatism  of  heart,  306,  338 

cardiac  plethysmograph,  289 

cardiac  vagus,  324,  338 

heart,  electrical  variations,  332 

neart,  suspension,  289 

myogenic  theory,  307,  314 

nervi  erigentes,  355,  367 
GASSENTI,  circulation,  166 
GASSER,  ganglion  of,  328,  354 
GAULE,  diastole,  208 

diastolic  aspiration,  212 

intracardiac  pressure,   207,  212,   214, 
220 

normal  physiological  solution,  295 

pressure  of  blood,  254 
GAUTIER,  anaerobic  organisms,  69 
GEGENBAUER,  lymphatic  vessels,  508 
GEPPERT,  blood  gas,  284,  400,  474 

muscular  work,  470 

respiration  504 

GERLACH,  bronchial  muscle,  442 
GIANNUZZI,  cardiac  vagus,  332 
GIBBES,  haemolymphatic  glands,  557 
GIBSON,  periodic  respiration,  492,  504 
GIERKE,  respiratory  centre,  446,  504 
GIES,  artificial  respiration,  504 


G-IES,  osteomucoid,  40, 

protagon,  40 

GIRARD,  respiratory  centre,  446 
GLEY,  cardiac  sound,  200 

extra-systole,  321 

lymphatic  vessels,  517,  557 
GMELIN,  blood  gas,  377 
GOLDSTEIN,  tachypnoea,  471 
GOLGI,  haemorrhage,  152 
GOLTZ,  automatism  of  heart,  305,  337 

blood  pressure,  254 

cardiac  vagus,  336 

diastole,  209 

hyperaemia,  paralytic,  345 

intracardiac  pressure,  208,  214 

reflex  inhibition  of  heart,  336 

vaso-dilatators,  350,  367 

vasomotor  centres,  362,  364,  366 
GOOD  ALL,  spleen,  551 

thymus,  558 
GOTHLIN,  normal  physiological  solution, 

296,  338 
GRAHAM,  colloids  and  crystalloids,  21 

diffusion  of  gases,  379 
GRAM,  solution  of,  103 
GRANCHER,  leucocytes,  116 
GRANDIS,  elimination  of  C02,  391 
GRASHEY,  dicrotic  wave,  284 
GRASSI,  mosquitoes  and  coagulation,  124 
GRAUPNER,  auriculo-ventricular  bundle, 

315 

GRAWITZ,  blood,  121 
GREER,   J.    R.,   lymph  formation,   52*5, 
559 

salivary  glands,  558 
GREHANT,  residual  air,  423 
GRIFFINI,  spleen,  557 
GRISELINI,  circulation,  166 
GROSS,    normal   phvsiological    solution, 

297 

GRUBER,  cell,  rhizopoda,  13 
GRUNMACH,  cardiograph,  223 

latent  systole,  206 

velocity  of  blood  stream,  273 
GRUTZNER,  vascular  reflexes,  360,  367 

vaso-constrictors,  349 

vaso-dilatators,  351 
GRYNS,  serum,  osmotic  pressure,  144 
GSCHEIDLEN,  quantity  of  blood,  99 
GUERICKE,  air  pump,  371 
GULLAND,  spleen,  551,  556,  558 
GUNTHER,  circulation  of  blood,  162 
GURBER,  plasma,  mineral  matter,  132 

respiratory  gases,  389 
GURBOKI,  cardiac  vagus,  335 
GURWITSCH,  spleen,  552,  558 
GUTHRIE,  C.  C.,  blood  pressure,  284 

blood  pressure  and  respiration,  439 

coronary  pressure,  339 

red  blood-corpuscles,  122 

HADLEY,  P.  B.,  galvauotaxis,  90 
HAECKEL,  the  cell,  13 


580 


PHYSIOLOGY 


HAECKEL,  protista,  56 
HAESER,  vital  capacity,  423 
HAFIZ,  vaso-constrictors,  349 
HALDANE,  J.  S.,  alveolar  C02,  439 
barometric  pressure  and  respiration, 

439 

blood  gases,  391,  400,  401 
Gheyne-Stokes  breathing,  504 
haemo-globinometry,  121 
regulation  of  respiration,  439,  504 
HALES,  blood  pressure,  241 
"  pneumatic  "  chemistry,  373 
velocity  of  blood  in  capillaries,  263 
HALLEU,  activity  of  heart,  299 
auriculo-ventricular  valves,  192 
circulation  of  blood,    160,   164,    167, 

172,  341 
diastole,  208 

"elementa  physiologiae,"  9 
intercostal  muscles,  410 
mechanics  of  respiration,  403 
respiration,  429,  439 
HAM,  E.,  blood,  122 
HAMBERGER,   intercostal  muscles,  410, 

412,  439 

semilunar  valves,  187 
HAMBURGER,  blood  gases,  386 
lymph  formation,  526,  584 
molecular  concentration,  142,  147 
osmotic  pressure  and  ions,  121,  155 
osmotic  pressure  of  plasma,  143 
osmotic  pressure  of  serum,  144 
semilunar  valves,  187 
HAMMARSTEN,  coagulation  of  blood,  135 
enzymes,  32 
lymph  gases,  514 
nucleoproteins,  thymus,  545 
physiological  chemistry,  39 
proteins  of  plasma,  128 
salted  plasma,  128 
HAMMEKSCHLAG,  sp.  gr.  of  blood,  95 
HANRIOT,  lipase  of  blood,  127 
HARDY,  colloidal  solution,  40 

leucocytes,  113 
HARRIS,  T.  F. ,  proteins,  40 
HARRISON,  haemolymphatic  glands,  557 
HARTLEY,  P.,  fat  of  liver,  41 
HARTWELL,    intercostal  muscles,    412, 

414,  439 

HARVEY,  afferent  nerves  of  heart,  335 
circulation,  166,  169,  171 
diastole,  208 
heart  beat,  222,  225 
heart  sounds,  196 
rate  of  blood  stream,  259 
respiration,  371 
systole,  182 

HARWOOD,  W.  S.,  botany,  63 
HASLAM,  H.  C.,  proteins,  40 
HASSE,  diaphragm,  410 
HASSELBACH,  blood  gases,  395 
HAWK,  P.  B.,  blood  and  muscular  work, 
122 


HAYCRAFT,  blood,  anti-coagulants,  124 

systole,  186 

HAYEM,  coagulation  of  blood,  134 
haemacytometry,  103 
haematoblasts,   100,  118,  121 
haemorrhage,  152 

HEDBLOM,  C.  A.,  blood  pressure,  284 
HEDIN,  centrifuge,  98 
enzymes  in  blood,  156 
haematocrite,  104,  121 
molecular  concentration,  147 
HEDON,  isolation  of  heart,  291 
HEFFTER,  oxygen  and  activity  of  heart, 

293 
HEGER,  P.,  diapedesis,  179 

vascular  reflexes,  355 
HEIDENHAIN,  accelerators  of  heart,  328 
cardiac  vagus,  218,  324,  325,  329 
formation  of  lymph,  519,  557 
lymphagogues,  523 
megacaryocytes,  535 
periodic  respiration,  494 
quantity  of  lymph,  514 
respiratory  centre,  445 
Stannius  heart,  300 
vascular  reflexes,  360,  361 
vaso-constrictors,  349 
vaso-dilatators,  351 
vasomotor  centres,  363 
HEIN,  periodic  respiration,  502 
HEINRICIUS,    mechanics  of  circulation 

and  respiration,  435,  439 
HEITZMANN,   structure   of  protoplasm, 

17 

HELLER,  contraction  of  lymphatics,  517 
HELLRIEGEL,  nitrifying  bacteria,  58 
HELMHOLTZ,  conservation  of  energy,  5 

resonators,  197 
VAN  HELMONT,  intercostal  muscles,  411 

respiration,  371,  373,  400 
HENDERSON,  J.,  thymus,  558 
HENDERSON,  Y.,  heart  volume,  231 
HENLE,    blood-vessels,    active    move- 
ments of,  341 
cardiac  vagus,  323 
intercostal  muscles,  412 
myocardium,  182 
HENEIQUES,    vagi    and   gas  exchange, 

392 

HENRY,  gas  law,  378,  384 
HENSEN,  plankton,  82 
HERBST,  quantity  of  blood,  98 
HERICOURT,  toxicity  of  blood,  153 
HERINO,  Ed.,  circulation  time,  282 
BERING,    Ew.,    automatic    control    of 

respiratory  rhythm,  459,  503 
blood  and  respiratory  rhythm,  480,  486 
cardiac  vagus,  336 
diapedesis,  177 
experimental  apnoea,  486 
inspiratory  centres,  456 
living  matter,  metabolism,  86,  89 
oscillations  of  vascular  tone,  500 


INDEX  OF  AUTHOES 


581 


HERING,  Ew.,  trigemiims  and  respira- 
tion, 464 

Traube-Hering  waves,  343 
HERING,    H.    E.,    auriculo-ventricular 

bundle,  315,  317,  337 
cardiac  nerves,  310 
cardiac  vagus,  327 
isolated  heart,  291 
resuscitation  of  heart,  298 
HERING.     P.,     blood    and    respiratory 

rhythm,  480,  486 

HERMANN,     demarcation     and     action 
'  currents,  332 
galvanotaxis,  81 
gases  of  expired  air,  397 
lungs  of  newborn,  405,  439 
oxygen  and  muscle  (frog),  68 
physiology,  handbook, -9 
tissue  respiration,  394 
HEROPHILUS,  arterial  pulse,  264 
lacteals,  171 
respiration,  370 

HERTWIG,  0.,  cell  and  tissues,  39 
HERTWIG,  R.,  amoeba,  13 

centersome,  13 
HERZEN,  spleen,  553 
HESSE,  myocardium,  182,  190 
HEWSON,  coagulation,  132,  135 
leucocytes,  93 
respiration,  373 
HIFFELSHEIM,  heart-beat,  225 
HILL,    L.,    blood    in    high    barometric 

pressure,  401 

residual  arterial  pressure,  284 
respiration  and  circulation,  439 
HIRSCHFELD,  platelets,  119 
HIRSCHFELDER,    A.    D.,    extra  -  systole, 

339 

HIRT,  spleen,  552 
His,  W.,  lymphatic  system,  179 
His,  jun. ,  auriculo-ventricular  bundle, 

315 

embryonic  heart,  308 
HOBER,  physical  chemistry,  121 
VON  HOESSLIN,  spirometry,  423 
HOFER,  amoeba,  14 
HOFF,  VAN  T',  solutions,  141 
HOFFA,  delirium  cordis,  321 
HOFFMANN,    K.,   circulation   of  blood, 

170 
HOFMANN,  auriculo-ventricular  bundle, 

317,  337 
HOFMEISTER,  enzymes,  29 

proteins,  25 
HOLMGREN,  blood  gases,  380 

circulation  in  capillaries,  173,  178 
HOLT,  E.  B.,  phototaxis,  90 
HOOK,  experimental  apnoea,  476 

respiration,  371,  400 
HOOKER,  heart,  339 

post-mortem  lymph,  515,  558 
HOORWEG,  dicrotic  wave,  269 
HOPKINS,  F.  G.,  ammo-acids,  40 


HOPKINS,  F.  G.,  proteins,  40 
HOPPE-SEYLEU,    blood   gas,    377,    380, 
400 

diffusion  of  gas,  379 

haemoglobin,  105 

lecithin.  35 

leucocytes,  117 

oxyhaemoglobin,  383 

physiological  chemistry,  39 

plasma  and  corpuscles,  125 

plasma  soaps,  130 

proteins,  24 

stromata,  106 

tissue  respiration,  393 
HORBACZEWSKI,  spleen,  552 
HORNE,  coagulation,  137 
HOWELL,  W.  H.,  heart,  338,  339 

heart  inhibition,  339 

megacaryocytes,  535,  584 

proteins  of  blood,  156 

vagus  action,  339 
HUFNER,  haemoglobin.  107 

oxygen  of  blood,  383,  420 

spectro- photometry,  111 
HUGHES,  W.  T.,  haemolytic  lymph,  559 
HULTKRANTZ,  respiration,  418 
HUMBLET,  auriculo-ventricular  bundle 

315,  337 

v.  HUMBOLDT,  oxygen  and  heart,  293 
HUNT,  REID,  cardiac  nerves,  331 
HUNTER,  blood,  94 

invertebrate  heart,  311 
HUNTER,   W.,  cerebral  vascular  nerves 

368 
HURTHLE,  cardiograph.  222 

dicrotic  wave,  269 

haemodromometer,  259,  284 

intracardiac  pressure,  201 

latent  systole,  206 

manometer,  244 

sphygmomanometer,  250 

viscosity  of  blood,  151 
HURTLEY,    W.  H.,    sulph-haemoglobin, 

122 
HUTCHINSON,   intercostal  muscles,  412, 

439 

spirometry,  422,  439 
types  of  respiration,  416,  439 
HYDE,  heart,  automatic  control,  211 

respiratory  centre,  504 
HYRTL,  semilunar  valves,  187 

INGENHOUSZ,  plant  metabolism,  54 

JACKSON,  H.  C.,  splenectomy,  558 
JACOBSON,  hydrodynamics,  235 

intrathoracic  pressure,  427 

plasma,  jecorin,  130 

venous  pressure,  253 
JACQUET,  tissue  respiration,  393,  400 
DE  JAGER,  diastole,  209,  214 

intracardiac  pressure,  207,  214 
JAKOWICKI,  coagulation  of  blood,  138 


582 


PHYSIOLOGY 


v.  JAKSCH,  reaction  of  blood,  96 
JAPPELLI,  tistula  of,  513 

polypnoea,  471 

post-mortem  lymph,  515 
JENSEN,  cblpidinm  colpoda  and  inani- 
tion, 66 

geotaxis,  77 
JOHANSSOHN,  cardiac  vagus,  218,  326 

vasomotor  centres,  366 
JOLYET,  rate  of  blood  stream,  238 
JONES,  WHARTON,  vascular  rhythm,  343 

KABIEIISKI,  vasomotor  centres,  364 
KAISER,  extrasystole,  321 

heart  stimuli,  321 
KANTHAOK,  leucocytes,  113 
KATZBNSTEIN,  respiratory   movements, 

466 

KAUFMANN,  periodic  respiration,  502 
KAYA,  R.,  phospho- proteins,  41 
KAZEM-BECK,  depressor,  334 
KEITH,  heart  beat,  224 
KELLER,  hydrostatic  pressure,  72 
KEMP,  G.  T.,  blood-platelets,  121 
KENDALL,  vasodilatators,  351 
KENT,    STANLEY,   auriculo  -  ventricular 

bundle,  314 
KEYT,  latent  systole,  206 

velocity  of  blood  .stream,  273 
KING,  W.  0.  K.,  blood,  401 
KITASATO,  immunisation,  154 
KIWISCH,  heart  beat,  225 
KLEEN,  vascular  reflexes,  360 
KLEIN,  lymphatics,  509,  530 
KLEINBNBERG,   examination   of  blood, 

120 

KLIKOWICZ,  formation  of  lymph,  525 
KLUG,  automatic  control  of  heart,  211 

cardiac  vagus,  333 

oxygen  and  heart,  293 
KNIGHT,  geotaxis,  77 
KNOLL,  cardiograph,  223 

experimental  apnoea,  476 

heart,  suspension,  291 

pneumoplethysmograph,  425,  491 

vascular  reflexes,  360 
KOCH,  anthrax  bacilli,  71 
KOCHER,  splenectomy,  555 
'  KOCHS,  potential  life,  67 
EOHLUAUSCH,    electrical    conductivity, 

149 

V.^KOLLIKER,  spleen,  546,  549,  552 
KONIG,  tuning-fork,  6 
KONOW,  cardiac  vagus,  333 

depressor,  335 

vasomotor  centres,  364 
KOPPE,  molecular  concentration  of  blood, 
147,  155 

platelets,  119 

KORSCHINSKI,  heterogenesis,  52 
KOSSTCL,  histones,  106,  117 

nucleus,  39 

proteins,  25 


KOSSEL,  proteins  of  cell,  39 

structure  of  proteins,  25 
KOSTEK,  depressor,  335 
KOWALEWSKI,  vasomotor  centres,  365  { 
KRATSCHMER,  trigeminus  ^and  respira-' 

tion,  464 
KREHL,  auriculo-ventricular  valves,  194 

diastole,  212,  215,  231 

diastolic  aspiration,  209 

myocardium,  182, -184 

myogenic  theory,  314 
VON  KRIES,  capillary  pressure,  253 

circulation  time,  283 

pulse,  284 
KROGH,  blood  gases,  395 

nervous   system  and    gas   exchange, 

392,  420 

KRONECKER,  cannula  (perfusion),   288, 
337 

co-ordination  of  heart,  321,  337 

heart  muscle,  318,  321 

mechanics  of  respiration  and  circula- 
tion, 435,  439 

normal  physiological  solution,  295 

periodic  respiration,  495,  502 

red  blood-corpuscles,  105 

respiratory  centres,  448 

transfusion  of  blood,  153 
KutJGER,  spleen,  551 
KRUSS,  spectrophotometer,  112 
KUHNE,  chemical  stimuli,  73 

electrical  stimuli,  80 

reaction  of  blood,  95 

thermal  tetanus,  77 
KULIABKO,  heart,  resuscitation,  298 
KUKLOW,  splenectomy,  555 
KURSCHNEK,  activity  of  heart,  231 

auriculo-ventricular  .valves,  192 

neurogenic  theory,  307 

presystole,  181 

Kiiss,  auriculo-ventricular  valves,  192 
KUSSMAUL,  asphyxia,  479 

LABORDE,  cardiac  centres,  336 
LAENNEC,  heart  sounds,  196 

mechanics  of  respiration,  403 
LAFFONT,  vasomotor  centres,  366 
LAGRANGE,  respiration,  375 
LAIDLAW,  P.  P.,  blood  pigments,  122 
LAMARCK,  biology,  1 

evolution,  48,  65 
LAMBERT,  urea  and  heart,  297 
LANCISI,  automatic  control  of  heart,  211 
LANDERGREEN,  asphyxia,  452 
LANDOIS,  autosphygmogram,  265,  283 

cardio-pneumatic  curves,  227 

intercostal  muscles,  412 

latent  systole,  206 

lungs,  movements,  426 

mechanics  of  respiration  and  circula- 
tion, 437 

pulse,  231 

reaction  of  blood,  96 


INDEX  OF  AUTHOKS 


583 


LANDOIS,  toxicity  of  serum,  153 

transfusion  of  blood,  153 

vasomotor  centres,  365 
LANGENDORFF,  asphyxia  and  heart,  304 

ciliary  ganglion,  310 

heart,  isolation,  291,  338 

normal  physiological  solution,  297 

oxygen  and  heart,  293,  338 

periodic  respiration,  493,  501,  504 

respiratory  centres,  447,  451 

stimulation  of  heart,  321 
LANGERHANS,  thymus,  542 
LANGLEY,  vaso-dilatators,  354 
LAPICQUE,  spleen,  551 
LAPLACE,  respiration,  400 
LASSAR,  reaction  of  blood,  96 
LATSCHEMBERGER,  mechanics  of  respira- 
tion and  circulation,  434 

vasomotor  centres,  363 
LAUDENBACH,  lymphoid  organs,  558 
LAVOISIER,  animal  respiration,  54,  374, 
400 

chemistry  of  respiration,  396 

indestructibility  of  matter,  5 

modern  chemistry,  396 

volume  of  expired  air,  398 
LAZARUS-BARLOW,  formation  of  lymph, 

526 

LEAVENWORTH,  proteins,  40 
LEBER,  chemotaxis,  leucocytes,  178 
LEE,  F.  S.,  phototaxis,  90 
LEEUWENHOEK,  anabiosis,  66 

capillary  circulation,  172 

red  blood-corpuscles,  93 
LEFEVRE,  systolic  aspiration,  210 
LEGALLOIS,  pulmonary  vagus,  157 

respiratory  centre,  444 
LEGROS,  cardiac  vagus,  324 
LEHMANN,  blood,  94 

quantity  of  blood,  98 
LEPINE,  glycolysis  in  blood,  127 

vasomotors,  352 

LEROYENNE,  rate  of  blood  stream,  275 
LESEM,  W.  W.,  protagon,  40 
LESSER,  transfusion  of  blood,  153 
LEUBE,  periodic  respiration,  502 
LEVENE,  P.  A.,  autolysis,  40 

edestin,  40 

proteose,  40 
LEWANDOW.SKY,  nervous  mechanism  of 

respiration,  504 
LEWIS,  T.,  heart  rhythm,  231 

sphygmograni,  284 

thoracic      movements      and      blood  - 

pressure,  284 

LEYDIG,  haemolymphatic  glands,  557 
LIEBERKUHN,  glands  of,  528 

leucocytes,  115 
LIEBIG,  animals  and  plants,  55 

oxygen  of  blood,  383 
LIEBREICH,  protagon,  35 

reaction  of  blood,  95 
LILIENFELD,  coagulation  of  blood,  136 


LILIENFELD,  lymphocytes,  117 

molybdate  test,  39 

platelets,  118 

LILLIE,  R.  S.,  electrical  convection,  90 
v.  LIMBECK,  lyinphagogues,  525 

osmotic  pressure  of  blood,  146 

pathology  of  blood,  155 
LINDHAGEN,  pulmonary  vagus,  459 
j    LINGLE,  D.  J.,  heart  rhythm,  231 

ions  and  heart,  338 
LINNAEUS,  animals  and  plants,  53 

immutability  of  species,  45 
LITTEN,  marrow,  539 

spleen,  556 

I   Lo  BIANCO,  marine  biology,  90 
|    LOCK,  R.  H.,  variation,  63 
I    LOCKE,  F.  S.,  glucose  and  heart,  296, 
338,  339 

normal  physiological  solution,  296,  338 
'   LOEB,  cell  theory,  12 

galvanotaxis,  80 

general  physiology,  90 

geotaxis,  77 

heliotaxis,  79 
I    LOEWY,  acapnia,  475,  504 

pulmonary  gas  exchange,  392,  400 

respiratory  centres,  464 

trigeminus  and  respiration,  465 

water  of  alveolar  air,  391 
LOMBARD,  W.  P.,  heart  rhythm,  231 
Lo  MONACO,  thymus,  542,  558 
LONGET,  bronchial  muscle,  442 

intercostal  muscles,  411 

respiratory  centre,  444 

"  Traite  de  physiologic,"  9 
LORRY,  respiratory  centre,  444 
LORTET,     sphygmograms     and     tachy- 

grams,  276 

LOTSY,  doctrine  of  descent,  62 
LOVEN,  cervical  plexus,  349 

negative  pulse,  227 

vascular  reflex,  356,  359,  367 
LOWER,     auriculo  -  ventricular    valves, 
192,  400 

respiration,  372,  400 
LOWIT,  platelets,  118 
LUBARSCH,  chemotaxis,  leucocytes,  178 
LUCHSINGER,  periodic  respiration,  495, 
501,  504 

vaso-dilatators,  351 
LUCIANI,  active  vaso-dilatation,  347 

active  diastole,  208,  214,  231 

activity  of  heart,  300,  337 

auriculo- ventricular  valves,  194 

automaticity,  85 

automaticity  of  heart,  215 

automatism   of    respiratory   rhythm, 

,.   498,  504 

cardiac  vagus,  217 

excitability  and  sensibility,  45 

experimental  apnoea,  480,  484 

expiration,  419 

haemodromometer,  258 


584 


PHYSIOLOGY 


LUGIANI,  human  bulb,  445 

inanition,  65 

inspiratory  centres,  456 

intra-abdominal  pressure,  429 

intrathoracic  pressure,  407 

intrathoracic     and    intra  -  abdominal 
pressures,  231,  427 

leucocytes,  116 

mechanics  of  respiration  and  circula- 
tion, 430,  439 

minimal  life,  67 

oesophageal  sound,  228,  429 

oesophageal  sphygmograms,  228 

oxygen  and  heart,  293 

periodic  respiration,  494,  501 

periodic  rhythm  of  heart,  302 

plethysmograms  and  tachygrams,  280 

pulmonary  vagus,  458 

rectal  explorer,  429 

red  blood-corpuscles,  105 

respiratory  movements   in  asphyxia, 
425,  448 

ribs,  408 

section  of  phrenics,  435 

semilunar  valves,  189 

staircase  phenomenon,  318 

tonographic  apparatus,  288 

transfusion  of  blood,  153 
LUCKHARDT,  A.  B.,  lymph  formation, 

526,  559 

LUDWIG,    accelerated   cardiac    rhythm, 
181 

accelerators  of  heart,  327,  338 

auriculo- ventricular  valves,  192 

blood  pressure,  241,  254 

cardiac  ganglia,  299 

cardiac  systole,  182,  187 

delirium  cordis,  321 

depressor,  333,  360,  367 

formation  of  lymph,  519 

gases  of  blood,  367,  377,  379 

glandular  secretion,  391 

haemodromometer,  257 

heart  beat,  224 

heart  sounds.  197 

hydrodynamics,  189 

kymograph,  242 

lymphatic  circulation,  518,  522 
,    lymphatic  pressure,  516,  557 

mechanics  of  respiration,  439 

myocardium,  182 

normal  physiological  solution,  295 

physiology,  text-book,  231 

pulmonary  catheter,  388 

recording  manometer,  207 

serous  cavities,  509 

splanchnic  nerve,  347 

vasomotor  centres,  347,  362,  366 
LUNIN,  assimilation  of  inorganic  matter, 

62 

LURIA,  respiratory  reflex,  466 
LTJSCHKA,  thorax,  409 
LUSSKY,  H.  0.,  lymph,  559 


LYON,  excitation,  90 

geotropism,  90 

rheotropism,  90 
LYONET,  apparatus  of,  173 

MAAR,  nerves  and  gas  exchange,  392 
McCoLLUM,  nuclein  synthesis,  41 
M'CuRDY,  F.  H.,  blood  pressure,  284 
MACH,  sensations,  6 
MACKENZIE,  venous  pulse,  203 
MACLEOD,    J.    J.    R.,    blood    at    high 

pressures,  401 

MACNALTY,  S.,  heart  rhythm,  231 
MACWILLIAM,  automatism  of  heart,  306 

cardiac  vagus,  326 

chloroform,  heart,  338 

delirium  cordis,  321 

rigor  mortis,  heart,  231 
MAFFUCCI,  spleen  and  liver,  556 
MAGENDIE,  auriculo-ventricular  valves, 
196 

cardiac  diastole,  213 

circulation,  341 

haemodiastase,  134 

heart  sounds,  196 

intercostal  muscles,  411 

vascular  reflexes,  359 
MAGGIOHANI,  spleen  and  liver,  556 
MAGNUS,  G.,  blood  gases,  377,  400 
MAGNUS,  R.,  oxygen  and  heart,  294 

vagus,  553 
MAISSIAT,  intercostal  muscles,  411,  439 

thoracic  respiration,  417 
MALASSEZ,  haemacytometer,  102,  116 

isotonic  solution,  143 
MALERBA,  cardiac  vagus,  323 
MALFATTI,  nucleus,  39 
MALPIGHI,  capillary  circulation,  172 

corpuscles,  spleen,  547 

fibrin,  97 

red  blood-corpuscles,  93 

structure  of  lungs,  403 
MANCA,  osmotic  pressure  of  blood,  146, 

155 

MANTEGAZZA,  coagulation,  134 
MARAGLIANO,  vascular  reflexes,  357 
MARCACCI,  ANT.,    intercostal  muscles, 

414,  439 
MARCACCI,  ART.,  extrasystole,  321 

tissue  lymph,  527 
MARCHAND,  respiration,  376 
MARCKWALD,    blood    and    respiratory 
rhythm,  494 

periodic  respiration,  496,  502,  504 

respiratory  centres,  448,  464 

trigeminus  and  respiration,  465 
MAREY,  arterial  pressure,  241,  248,  433 

cardiac  myograph,  291,  337 

cardiograph,  223 

cardiographic  sound,  200 

circulation  of  blood,  231,  284 

diaphragm,  433 

heart  beat,  224,  225 


INDEX  OF  AUTHOKS 


585 


MAREY,  intracardiac  pressure,  201 

latent  systole,  206 

metallic  manometer,  244 

refractory  period,  320,  337 

pneumograpli,  415 

recording  tympanum,  201 

sphygmograph,  264,  284 

sphygmomanometer,  247 

sphygmoscope,  205 

vascular  walls,  241 

waves,  241 

MARIANNINI,  heart  beat,  222 
MARIETTE,  anabiosis,  66 
MARIOTTE,  gas  law,  378 
MARINESCO,    respiratory    centre,    446, 

504 
MARKS,  H.  K. ,  vasomotor  centres,  368 

vasomotor  reflexes,  368 
MARSHALL,  A.  K.,  bionomics,  63 
MARTIGNI,   COLLARD    DE,    respiration, 

377 
MARTIN,  cerebrum  and  respiration,  453 

intercostal  muscles,  412,  414,  439 

isolation  of  heart,  291 

heart,  oxygen,  401 

MARTIN,  E.  G.,  heart,  potassium,  338 
MARTIUS,  normal  physiological  solution, 
295 

oesophageal  pulsations,  230 
MASCAGNI,  formation  of  lymph,  519 

serous  cavities,  509 
MASIUS,  vascular  reflexes,  357 

vasomotor  centres,  366 
MASOIN,  cardiac  vagus,  324 

intercartilaginous  muscles,  415 
MASSART,    chemotaxis,   leucocytes,    75, 
178 

phagocytosis,  116 

MATTHEWS,  S.  A.,  blood  pressure,  284 
MATJROCORDATO,  circulation,  160 
MAYER,  viscosity  of  blood,  151 
MAYER,  J.  R.,  conservation  of  energy,  5 

metabolism  of  green  plants,  55 
MAYOW,  intercostal  muscles,  411 

respiration,  372,  377,  400 
MECKEL,    auriculo  -  ventricular  valves, 

192 

MEEK,  W.  J.,  heart,  339,  340 
MEISSNER,  intercostal  muscles,  412 
MELLANBY,  J.,  coagulation",  156 

serum,  156 

MELTZER,  C.,  vasomotor  nerves,  368 
MELTZER,   S.   J.,   artificial  respiration, 
504 

cardiac  nerves,  331 

vasomotor,  368 
MENDEL,  L.  B.,  edestin,  40 

lymph,  558 

splenectomy,  558 
MENDEL,  evolution,  52 

post-mortem  lymph,  515 
MENDELEJEFF,  periodic  system,  20 
MENDELSSOHN,  thermotaxis,  78 


MERKEL,  periodic  respiration,  502 
MERRIMAN,  C.  IL,  mutation,  63 
MERUNOWICS,      normal      physiological 

solution,  295 
METSCHNIKOFF,  chemotaxis,  75 

inflammation,  179 

phagocytosis,  18,  115 
MEYER,  blood  gas,  380,  383 

cardiac  vagus,  324 

experimental  apnoea,  479 

respiration,  377,  400 
MICANZIO,  circulation,  166 
MICHAELIS,  fats,  blood,  127 
MIESCHER,  apnoea,  true  and  false,  477, 
488,  504 

leucocytes,  117 

nucleo-proteins,  24,  39 

plasma,  histogenic  substances,  126 
MILLER,  J.  R.,  galvanotropism,  90 
MILLON,  protein  reaction,  22 
MILLS,    WESLEY,    cardiac   vagus,    324, 

326 

MILNE-EDWARDS,    comparative   physi- 
ology, 9 

division  of  labour,  91 

lymphatic  system,  509 
MINCK,  diastolic  aspiration,  212 
MIRTO,  depressor  nerve,  335 
MISLAWSKI,  respiratory  reflex,  466 

vasomotor  centres,  366 
MOENS,  velocity  of  pulse  wave,  273,  284 

waves,  241 

MOHL,  protoplasm,  11 
MOLESCHOTT,  cardiac  vagus,  322 

tissue  respiration,  394 
MOLISCH,  proteins  reaction,  22 
MONTENOVESI,  spleen  and  liver,  556 
MONTI,  test  for  phosphorus,  39 
MOORE,  sugar  reaction,  36 
MOORE,  A.,  geotropism,  90 

lymph  hearts,  558 
MOORE,  B.,  spleen,  554,  558 
MORAT,  cardiac  vagus,  323 

cervical  sympathetic,  349,  353,  367 

nerves  of  neck  (rabbit),  334 

vascular  reflexes,  361,  367 

vasomotor  centres,  366 

vasomotor  nerves,  351,  353 
MORAWITZ,  coagulation,  156 

thrombokinase,  139 
MORGAGNI,  spleen,  555 
MORGAN,  Th.  H.,  evolution,  63 
MORNER,  ovo-nmcoid,  126,  129 
Mosso,  A.,  acapnia,  474 

asphyxial  pause,  452 

blood  pressure,  253,  284 

cardio-pneumograms,  227,  231 

diastolic  aspiration,  210 

inspiratory  centres,  456 

periodic  respiration,  493 

plethysmograph  and  plcthysmograms, 
279,  344,  367 

pulse,  231,  284 


586 


PHYSIOLOGY 


Mosso,  A.,  respiration  at  high  altitudes, 

472,  499 
luxus  respiration,  472 


sphygmomanometer,  284 
thoracic  and   abdo 


thoracic  and   abdominal    respiration, 
418,  439 

tidal  air,  423 

tonicity  of  respiratory  muscles,  504 

toxicity  of  heterogeneous  blood,  153 

vascular  tone,  346 

voluntary  apnoea,  480,  483 
Mosso,  U.,  periodic  respiration,  494 

respiration  at  high  altitudes,  474 
MULDER,  blood,  94 
MULLER,  F.,  acapnia,  475 

respiration  at  high  altitudes,  504 

splenic  cells,  549 
MULLER,  J.,  blood  gases,  376 

cardiac  ganglia,  299 

coagulation,  135 

life,  3,  9 

mechanics  of  respiration  and  circula- 
tion, 436 

physiology,  .3,  9 

respiration,  376 

solution  of,  104 
MULLER,  W.,  oxygen  of  blood,  384 

respiratory  valves,  420 
MUNK,  I.,  lymph,  514 

urea  of  blood,  129 

MURE,    DE    LA,    locomotion    of    blood- 
vessels, 277 

MURRAY,  marine  biology,  81 
MURRI,  periodic  respiration,  502 
MYERS,  W.,  erythrocytes,  121 

NAGEL,  W.,  physiology,  handbook,  9 
NAGELI,  adaptation,  65 

evolution,  49,  62 
NAMIAS,  heart  beat,  222 
NASINI,  solutions,  155 
NASSE,  blood,  94 

extraction  of  gas,  377 

glycolysis  in  blood,  127 
NEANDER,   apnoeic    respiratory   pause, 

482,  504 

NEGA,  systolic  aspiration,  210 
NEGRI,  red  blood-corpuscles,  540 
NEILSON,  C.  H.,  enzyme  action,  40 
'fats,  40 

inversion  of  starch,  40 
NEUMANN,  marrow,  534,  557 

spleen,  550 
NEUMEISTER,  physiological  chemistry, 

39 

NEWMAN,  H.  H.,  heart,  401 
NICOLAIDES,  rate  of  circulation,  260 
NOBBE,  nitrifying  bacteria,  58 
NOLF,  coagulation,  140 
NOLL,  lymphatic  pressure,  516 
NOLL,  F.,  botany,  62 

heliotaxis,  79 

nitrifying  bacteria,  58 


NOTE  NAGEL,  lympathic  vessels,  512 
NOWAK,  expired  air,  397 
NUEL,  cardiac  vagus,  326 
NUTTALL,     bactericidal    properties     of 
blood,  154 

OEHL,  abdominal  vagi,  348 

cardiac  valves,  183,  191 

diastolic  aspiration,  212 

luminous  stimuli,  78 
OEHRWALL,  oxygen  and  heart,  293,  338 

tonographic  apparatus,  288 
ONIMUS,  cardiac  vagus,  324 
OPPEL,  spleen,  548 
OPPENHEIMER,  ferments,  40 
ORIBASUS,  pneumothorax,  403 
ORTH,  marrow,  539 

spleen,  556 

OSBORNE,  T.  B.,  proteins,  40,  41 
OSBORNE,    W.    A.,   oxygen   tension    of 

blood,  401 

OSLER,  platelets,  118 
OSTROUMOFF,  tissue  lymph,  527 

vasomotor  nerves,  351,  354 
OSTWALD,  catalysis,  31 

energetic  monism,  6 

viscosimeter,  151 
OTTO,  glucose  of  blood,  130 
OUSKOFF,  leucocytes,  114 
OWSJANNIKOW,  vasomotor  centres,  363 

PACINI,    mechanics  of  respiration  and 
circulation,  436 

solution  of,  103 
PACKARD,  A.  S.,  evolution,  63 
PAGLIANI,  diastolic  aspiration,  210 

neurogenic  theory,  308 
PALADINO,  auriculo-ventricular  bundle, 
314 

auriculo-ventricular  valves,  191,  231 

erythroblasts,  539 
PANUM,  cardiac  vagus,  332 

transfusion  of  blood,  153 
PAPPENHEIM,  platelets,  119 
PARCHAPPE,  active  diastole,  213 

auriculo-ventricular  valves,  192 
PASCHUTIN,  formation  of  lymph,  522 
PASTEUR,  aerobic  and  anaerobic  organ- 
isms, 69,  369 

ferments,  30 
PATON,  N.,  lymph,  514,  557 

spleen,  550,  556,  558 

thymus,  558 
PATRIZI,  bulb,  inhibitory  centres,  452 

periodic  respiration,  493 

pulmonary  vagus,  463 

rate  of  pulse  wave,  273,  284 

vascular  reflexes,  358,  367 
PAULY,  Darwinism  and  Lamarckisin,  62 
PAVY,  glycogen  of  blood,  131 
PAWLOW,  cardiac  nerves,  338 

quantity  and  pressure  of  blood,  255 
PEARL,  R.,  galvanotaxis,  90 


INDEX  OF  AUTHOKS 


587 


PEARSON,  K.,  evolution,  62,  63 
PECQUET,  lymphatic  system,  171,  505 
PEKELHARING,  coagulation,  139 
PELLACANI,  marrow,  539 
PESKIND,  S.,  blood-corpuscles,  121,  122 
PETRONE,  coagulation,  134 

erythrocytes,  540,  558 
PETTENKOFER,  nitrogen  of  blood.  387 
PEYER,  patches  of,  530 
PFEFFER,  chemotaxis,  75,  178 

osmotic  pressure,  141 

vegetable  physiology,  62 
PFEIFFER,  fats  of  blood,  130 
PFLUGER,  animals  and  plants,  89 

apnoea,  476,  477 

blood  gases,  377,  379,  387 

blood  and  respiratory  rhythm,   479, 
486 

cardiac  vagus,  324 

embryonic  heart,  308 

eupnoea,  472 

living  matter,  86,  89 

oxygen  and  life,  70 

pulmonary  catheter,  388 

splanchnic  and  respiration,  465,  504 

tissue  respiration,  86 
PICTET,  R.,  cold  and  life,  71 
PIEGEAUX,  heart  beat,  222 
PIEGU,  plethysmograph,  278 
PIKE,  F.  H.,  blood  pressure,  439 

heart,  339 

resuscitation  of  bulb,  504 
PILCHER,  J.  D.,  vasomotor  centre,  368 
PILLSBURY,  heart  rhythm,  231 
PIOTROWSKI,  vasomotors,  353,  367 
PIUTTI,  minimal  life,  67 
PLIMMER,  R.  H.  A.,  caseinogen,  40 

phosphoproteins,  24,  41 
PLINY,  splenectomy,  555 
PLOSZ,  nucleoproteins,  24 

strom  ata,  106 
POISEUILLE,  blood  pressure,  241 

circulation,  174,  341 

mechanics  of  thoracic  movements,  430 

plethysmograph,  278 
PONFIK,  transfusion  of  blood,  153 
PORTAL,  thoracic  duct,  171 
PORTER,  automatic  control  of  heart,  211 

automatism  of  heart,  306 

heart,  tonus,  339 

intracardiac  pressure,  206 

myogenic  theory,  313 

oxygen  and  heart,  293 

vasomotor  centre,  367,  368 
POSNER,  E.  R.,  protagon,  40 

proteins,  40 

POTAIN,  blood  pressure,  246 
POUCHET,  spleen,  556 
POULTON,  E.  B.,  bionomics,  63 
POTJLTON,  E.  P.,  respiration,  439 
PRAXAGORAS,  circulation,  162 
PREVOST,  blood,  94 

terminal  respiration,  452 


PREYER,  anabiosis,  66 

blood  gases,  387 

circulation  of  blood,  160 

haemin,  108,  121 
PRIESTLEY,  modern  chemistry,  94 

respiration,  373,  377,  400 
PRIESTLEY,  J.  G.,  respiration,  504 
PRZEWOSKI,  myocardium,  313 
PUGLIESE,  formation  of  lymph,  527 

lymphagogues.  523 
PUNNETT,  K.  C.,  merism  and  sex,  63 
PURKINJE,  myocardium,  313 

systolic  aspiration,  210 
PUSATERI,  depressor,  335 

QUETELET,  law  of,  48 

RABINOWITZ,  blood  pressure,  246 
RANSOM,  heart,  invertebrates,  311 
RANVIER,  coagulation,  134 

lymphatic  vessels,  505,  557 

myogenic  theory,  .'!07 

serous  cavities,  509 
RAOULT,  molecular  concentration.  142 

solutions,  141 
REBATEL,    automatic   control   of  heart, 

211 
VON  RECKLINGHAUSEN,  diapedesis,  175 

serous  cavities,  509 
REGNARD,  blood  gases,  387 
REGNAULT,  expired  air,  387,  417 
REGOLI,  calcium  and  coagulation,  137 
REICHERT,  E.  T.,  haemoglobin  crystals, 

122 

REID,  E.  W.,  haemoglobin,  122 
REID,  myocardium,  183 
REISET,  expired  air,  387,  417 
REMAK,  cardiac  ganglia,  299 

protoplasm,  17 
RESTELLI,  thymus,  542 
RETTGER,   L.  J.,   coagulation  of  blood, 

156 

RETXIUS,  nerves  in  spleen,  549 
RICHARDS,  A.  N.,  elastic  tissue,  40 
RICHARDSON,  R.,  vasomotor  reflexes,  368 
RICHET,  circulation,  165 

polypnoea,  471 

toxicity  of  blood,  153 

vasomotor  centres,  365 
RIDDLE,  0.,  blood  pressure,  284 
RIEGEL,  vascular  rhythm,  343 
RIGNANO,  evolution,  62 
RINDFLEISCH,  erythroblasts,  539 
RINGER,  normal  physiological  solution, 

296 
RIOLAN,  circulation,  170 

perisystole,  180 
RiVA-Rocci,  blood  pressure,  253 

sphygmomanometer,  251,  284 
RIVE,  latent  systole,  206 
ROAF,  H.  E.,  haemoglobin,  156 
ROBERTS,  Ff.,  blood  gas  analysis,  401 

oxyhaemoglobin,  401 


588 


PHYSIOLOGY 


ROBERTSON,    haemolymphatic    glands, 

557 
ROBERTSON,  T.  B.,  infusoria,  90 

protein  synthesis,  40,  41 
ROEVER,  cardiac  vagus,  336 
ROHMANN,  glycolysis  of  blood,  127 
ROHRIG,  fats  of  blood,  130 
ROKITANSKI,  spinal  respiratory  centres, 

447 

ROLLESTON,  diastole,  209 
ROLLET,  hydrodynamics,  235 

red  blood-corpuscles,  105,  121 
ROMBERG,  embryonic  heart,  308 

myogenic  theory,  314 
ROSENBACH,      blood     and     respiratory 
rhythm,  486 

periodic  respiration,  501 
ROSENHEIM,  glucose  and  heart,  338,  339 

protagon,  41 
ROSENSTEIN,  quantity  of  lymph,  514 

blood  and  respiratory  rhythm,  476 
ROSENTHAL,  cardiac  vagus,  324 

eupnoea,  471 

experimental  apnoea,  475 

general  physiology,  90 

inspiratory  muscles,  410 

intercostal  muscles,  410,  414 

intrathoracic     and      intra-abdommal 
pressure,  427 

phrenograph,  416 

pulmonary  vagus,  462,  503 

respiratory  capacity,  423,  439 

respiratory  centres,  468 

respiratory  quotient,  399 

superior    laryngeal    and   respiration, 

465 

Ross,  H.  C.,  leucocytes,  122 
ROSSBACH,  asphyxia  and  heart,  304 

cardiac  vagus,  218 

oxygen  and  heart,  293 
ROTH,  circulation,  161 

Vesalius,  179 

ROUANET,  heart  sounds,  196 
ROY,  accelerators  of  heart,  330 

blood  pressure,  245 

bronchio-dilatator  fibres,  442 

cardiac  plethysmograph,  289 

cardiac  systole,  182 

intracardiac  pressure,  201 

musculi  papillares,  202,  213 

sp.  gr.  of  blood,  95 

splanchnic  nerve,  348 

spleen,  554 

RUDBECK,  lymphatic  system,  505 
RUDINGER,  semilunar  valves,  187 
RUDOLPH,  mechanics  of  respiration, 

403 
RUFUS  OF  EPHESUS,  pulmonary  vagus, 

457 

RUSCH,  oxygen  and  heart,  294 
RUSCONI,  perivascular  lymphatic,  508 
RUSSEL,  A.  E.,  heart,  inhibition,  338 
RUTHERFORD,  accelerators  of  heart,  329 


RUYSCH,  fibrin,  97 

SABATIER,  intercostal  muscles,  411 
SABBATINI,  coagulation  of  blood,   137, 

155 
SACHS,  solution,  58 

starch  formation,  58 
SADLER,  vaso-constrictors,  349 
SALKOWSKI,  autolysis,  34 
SALOZ,  periodic  respiration,  502 
SALVIOLI,  marrow,  539 

serous  cavities,  511 

spleen,  550,  552 
SANDMANN,  bronchi, ,442 
SARPI,  venous  valves,  165 
DE  SAUSSURE,  plant  metabolism,  54 
SAVALIEW,  t hymns,  542 
SAVIOTTI,  vascular  rhythm,  343 
SCHAFER,  E.  A.,  blood,  121 

physiology,  text-book,  9,  12 

red  blood-corpuscles,  102 

spleen,  546,  554,  558 

vagus,  558 
SCHENCK,  cell  theory,  12 

respiratory  gases,  389 
SCHENK,  H.,  botany,  62 
SCHERER,  xanthine  bases  of  plasma,  130 
SCHIFF,  M.,  blood-vessels,  active  move- 
ments, 341,  367 

bronchial  muscles,  442 

hemi-section  of  spinal  cord,  452,  503 

respiratory  centres,  444,  446,  452 

spleen,  553 

vascular  tone,  oscillation,  500 

vasomotor  centres,  362,  364 
SCHIFF,  cardiac  vagus,   322,  327,  329, 
337 

cervical  plexus,  349 

periodic  respiration,  494 

vaso-constrictor  nerves,  349 
SCHIMPER,  botany,  62 
SCHLEIDEN,  cell  theory,  12 
SCHLESINGER,  vasomotor  centres,  364 
SCHLOESING,  blood  gas,  387 
SCHMALTZ,  pycnometer,  95 
SCHMIDT,  A.,  blood,  155 

blood  gases,  386 

coagulation,  134,  135 

extraction  of  gas,  380 

salted  plasma,  125 
SCHMIDT,  C.,  mineral  matter  of  plasma, 

131 

ScHMiDT-MtiHLEiM,  peptone  blood,  124 
SCHMIEDEBERG,  accelerators,  327,  338 

tissue  respiration,  393 
SCHNEIDER,  E.  C.,  blood  pressure,  284 
SCHNEIDER,  doctrine  of  descent,  62 
SCHRODER,  urea  and  heart,  297 
SCHROFF,  respiratory  centres,  447 
SCHULTZ,  cube  of,  111 

heart,  340 
SCHULTZE,  W.  H.,  cell,  13 

chemical  stimuli,  73 


INDEX  OF  AUTHOES 


589 


SCHULTZE,  W.  H.,  examination  of  blood, 
120 

leucocytes,  114 

red  blood-corpuscles,  101 

structure  of  protoplasm,  17 

temperature  and  plant  cells,  71 
SCHWANN,  cell  theory,  12 
SCHWARTZ,  foetal  apnoea,  478 
SCHWEIGGER-SEYDEL,   serous  cavities, 

509 
SCOTT,  F.  H.,  phospho-proteins,  24 

phosphorus  metabolism,  41 
•.   phosphorus  reaction,  39 
SCUDAMORE,  blood  gas,  377 
SCZELKOW,  blood  gas,  380 
S£E,  M.,  auriculo- ventricular  valves,  191 
SEEGEN,  expired  air,  397 
SEEHMANN,  C.,  muscular  work,  470 
SEEMANN,  haemolymphatic  glands,  557, 

558 

SEGUIN,  respiration,  375,  400 
SEIFERT,  osteomucoid,  40 
SELENSKI,.  marrow  and  spleen,  539 

spleen,  552,  585 
SEMOX,     laryngeal     respiratory    move 

ments,  421 
SENAC,  auriculo-ventricular  valves,  192 

circulation,  160 

heart  beat,  225 

intercostal  muscles,  411 
SENEBIER,  green  plants,  54 

respiration,  375,  400 
SERTOLI,  blood  gas,  385 
SERVETUS,  circulation,  160 
SETSCHENOW,  blood  gas,  380,  385 
SEVERANU,  splenectomy,  555 
SEWALL,  depressor,  335 
SHBREINQTON,  .locomotion  and  nervous 

system,  367,  466 

SHORE,  non-coagulable  lymph,  513 
SIBSON,  thoracic  respiration,  417 

thoracometer,  415,  439 
SIEBERT,  periodic  respiration,  501,  504 
SIEWERT,  isolation  of  heart,  292 
SIGHIUELLI,    automatic   control   of   re- 
spiratory rhythms,  460 

inspiratory  centres,  456,  504 
SILVIO,  Vesalius,  163 
SIMON,  blood,  94 
SKODA,  heart  beat,  225 
SMIRNOW,  periodic  respiration,  494 

vasomotor  centres,  366 
SMITH,  G.,  phototropism,  90 
SMITH,    LORRAINE,   oxygen    of    blood, 

391,  400 

SNELLEN,  vascular  reflexes,  356 
SOKOLOW,  periodic  respiration,  495,  501, 

504 

SOLLMANN,   T.,  resuscitation  of  heart, 
339 

vasomotor  centre,  368 
SOLTMANN,  vagal  tone,  337 
SOMMERBRODT,  cardiac  vagus,  336 


SPALLANZANI,  anabiosis,  66 

arterial  pulse,  277 

circulation,  341 

circulation  in  capillaries,  172 

respiration,  375,  400 

science  of  life,  3 
SPALLITTA,  depressor,  335 

vascular  reflexes,  375 
SPALTENHOLTZ,  thoracic  skeleton,  407 
SPIGEL,  intercostal  muscles,  412 
SPIRO,  muscular  work,  470 
SPRENGEL,  circulation,  165 

diastole,  208 
SPRING,  active  diastole,  213 

presystole,  181 

STAEDELER,  urea  and  heart,  297 
STAHL,  phlogiston,  374 
STAHL,  E. ,  chemotaxis,  74 

rheotaxis,  76 

STANLEY,  0.  0.,  blood  platelets,  121 
STANNIUS,  heart,  299,  337 
STARLING,  accelerators,  330 

cardiac  vagus,  326 

intracardiac  pressure,  201,  207 

lymph  formation,  520,  527,  557 

systolic  plateau,  206 
STEFANI,  automatic  control  of  respira- 
tory rhythm,  460 

cardiac  vagus,  218,  326 

diastole,  209,  231 

respiratory  centres,  456,  504 
STEINER,  arterial  pressure,  243 

depressor,  335 
STENBECK,  cardiac  vagus,  333 

depressor,  335 

vasomotor  centres,  364 
STERN,  terminal  respirations,  452 
STEWART,  G.  N.,  bulbar  centres,  504 

haemolysis,  122,  156 

red  blood-corpuscles,  121 
STIENON,  normal  physiological  solution, 

295 
STILLING,  active  movements  of  vessels, 

341 
STIRLING,  W.,  lymph-sac,  558 

myocardium,  318,  321 

normal  physiological  solution,  295 
STOKES,  heart- beat,  222 

periodic  respiration,  492 
STOPPATO,  thyrnus,  545 
STRASBURGER,  botany,  62 

chondrioderma,  16 

myxomycetes,  15 

phototaxis,  78 

tradescantia,  18 

STRASSBURG,  tissue  respiration,  395 
STRAUB,  normal  physiological  solution, 

297 

STRECKER,  oxygen  and  heart,  294 
VAN  DER  STRICHT,  megacaryocytes,  538, 

557 
STRICKER,  accelerators,  329,  337 

vasomotors,  355,  364,  367 


590 


PHYSIOLOGY 


SURMAY,    auriculo  -  ventricular   valves, 

192 

SVEHLA,  thymus,  545 
SWIFT,  J.  B.,  vasoniotor  centre,  368 

TALMA,  blood  pressure,  245 

heart  sounds,  197 

TANGL,  osmotic  pressure  of  blood,  144 
TAPPEINER,  quantity  and   pressure  of 

blood,  255 
TARCHANOFF,  cardiac  vagus,  324 

spleen,  554 

TAROZZI,  anaerobic  organisms,  68 
TARULLI,  thymus,  542,  558 
TAWARA,    auriculo-ventricular    bundle, 

314 
TAYLOR,  A.  E.,  protamiries,  41 

protein  synthesis,  40 
TEBB,  M.  C.,  protagon,  41 
TEDE.SCHI,  spleen,  551,  556,  558 
TENNER,  asphyxia,  479 
TERNE   VAN   DER    HEUL,    cardio-pneu- 

matic  curves,  228 
TERRY,  O.  P.,  galvanotropism,  90 
THANE,  diaphragm,  410 

sternum,  410 

THANHOFFER,  cardiac  vagus,  323 
THEBESIUS,  automatic  control  of  heart, 
211 

semilunar  valves,  187 
THIRY,  experimental  apnoea,  476 

vasoniotor  centres,  327,  362,  367 
THOMAS,  diapedesis,  115 
THOMA-ZEISS,  haemocytometer,  102 
THOMPSON,  marine  biology,  81 
THOMSON,  ALLEN,  heart,  181 

respiratory  muscles,  410,  411,  412 
TIEDEMANN,  blood  gases,  377 
TIGERSTEDT,  area  of  capillary  system, 
263 

automatism  of  heart,  306 

blood  pressure,  246 

cardiac  vagus,  218 

circulation  of  blood,  161,  231 

circulation  time,  283 

haemodromometer,  257 

heart  beat,  231 

heart,  work,  230 

intersystole,  202 

recording  spirometer,  425 

respiratory  gases,  390 

semilunar  valves,  190 

vascular  reflexes,  358 

velocity  of  blood,  263 
TIMOFEEW,  accelerators,  337 

cardiac  vagus,  333 
TISSANDIER,  balloon  ascent,  72 
TIZZONI,  splenectomy,  555,  557,  558 
TOLLIN,  circulation,  160,  166 
TORELLE,  E.,  phototaxis,  90 
TORRICELLI,  hydrodynamics,  233 
TORUP,  blood  gases,  385 
TOWLE,  E.  W.,  heliotropism,  90 


TRAMBUSTI,  erythroblasts,  536,  557 

megacaryocytes,  537 
TRAUBE,  artificial  cells,  147 

cardiac  vagus,  332 

inspiratory  muscles,  410 

oscillations  of  vascular  tone,  500 

periodic  respirations,  494,  498,  529 

pulmonary  vagus,  462 

vasoniotor  waves,  344 
TREMBLEY,  regeneration,  84 
TREVES,  pulmonary  vagus,  463 
TREVIRANUS,  biology,  1 
TRIPIER,  cardiac  vagus,  324 
TROMMER,  sugar  reaction,  36 
TSCHERMAK,  depressor,  335 
TSOHIR.TEW,  accelerators,  337 
TSHUEWSKY,  velocity  of  blood  stream, 

284 
TURNER,  heart  sounds,  196 

USTIMOWITSCH,  vasoniotor  centres,  366 

VAHLEN,  potassium  in  the  cell,  39 
VALENTIN,  active  vascular  movement, 
341 

velocity,  capillaries,  263 
VALSALVA,  mechanics  of  thoracic  move- 
ments, 429,  436 

sinus,  187 

VALVERDI,  circulation,  161 
VANLAIR,  vascular  reflexes,  357 

vasoniotor  centres,  366 
VAUQUELIN,  extraction  of  gas,  377 
VELLA,  splenectomy,  557 
VERNON,  H.  M.,  erepsin,  35 

tissue  respiration,  401 
VERWORN',  biogen  hypothesis,  90 

centres  and  oxygen,  394 

chemical  stimuli,  74 

galvanotaxis,  80 

general  physiology,  39,  87,  90 

muscle,  relaxation,  214 

phenomenalism,  7 

stentor,  15 

thalassicolla,  nucleus,  14 

thermotaxis,  78 

thigmotaxis,  76 
VESALIUS,  artificial  respiration,  403 

circulation,  162 

diastole,  208 

foetal  apnoea,  478 

intercostal  muscles,  411 

semilunar  valves,  187 
VESLING,  circulation,  166 

intercostal  muscles,  411 
VIAULT,  red  blood-corpuscles,  105 
VIERORDT,  auriculo-ventricular  valves, 
192 

blood  pressure,  245 

circulation  time,  283 

expired  air,  397 

haemocytometry,  102 

haemorrhage,  152 


INDEX  OF  AUTHOES 


591 


VIERORDT,  haemotachometer,  274 

mechanics  of  respiration,  439 

spectrophotometer,  111 

sphygmograph,  264 

tidal  air,  423 

velocity  in  capillaries,  263 
-  work  of  heart,  233 
VIEUSSENS,  auriculo-ventricular  valves, 
,  .       192 

annulus  of,  328,  354 
VINCENT,  haemolymphatic  glands,  557 

558 

VINCI,  LEONARDO  DA,  respiration,  370 
VIOLA,    serum,    electric    conductivity, 

150,  155 
VIRCHOW,  cell  theory,  12 

haematoidin,  109 

inflammation,  175 

spleen,  552 

VOGEL,  blood  gases,  377 
VOIT,  accelerators,  329 

blood  gases,  387 

negative  pulse,  227 
VOLKMANN,  blood  pressure,  253,  283 

haemodromometer,  257 

haemodynamics,  283 

ribs,  408 

respiratory  centres,  444 

velocity  in  capillaries,  263 

work  of  heart,  233 
Voss,  circulation,  166 
DE  VRIES,  H.,  molecular  concentration, 
141 

mutations,  51,  63 

species  and  varieties,  63 
VULPIAN,  splanchnic  nerves,  348 

vascular  reflexes,  359 

vasomotor  nerves,  348,  354,  367 
VULPIUS,  spleriectomy,  555,  558 

WAGNER,  accelerators,  337 

cardiac  vagus,  323 

circulation,  174 

pulmonary  vagus,  462 
WALAEUS,  circulation,  166 
WALDEN,   E.   C.,  normal  physiological 

solution,  338 
WALDENBURG,  blood  pressure,  245 

gasometric  apparatus,  484 

mechanics  of  respiration,  439 
WALLACE,  A.  R.,  Darwinism,  63 
WALLER,  A.,  cardiac  vagus,  329 

cervical  sympathetic,  342,  348 

diapedesis,  175 
WALLER,  A.  D.,  cardiac  vagus,  322 

periodic  respiration,  493 

sphygmograms,  266 

thoracic  respiration.  417 
WALSCHE,  thoracic  respiration,  417 
WALTER,  blood  gases,  380 
WARD,     R.     O.,     alveolar     air,     high 

altitudes,  439 
WARREN,  vasomotors,  352 


WASILEWSKY,  cardiac  vagus,  323 
WASILIEFF,  cardiac  vagus,  333 
WEBER,    E.    H.,    auriculo  -  ventricular 
valves,  192 

blood-vessels,  active  movements,  341 

cardiac  centres,  336 

cardiac  vagus,  322,  337 

mechanics  of  respiration,  436 

muscle,  elasticity,  347 

quantity  of  blood,  98 

sphygmographic  waves,  240,  282 

velocity  in  capillaries,  263 

wave  theory,  283 
WEBER,  W. ,  cardiac  vagus,  322 

wave  theory,  283 
WEBSTER,  heart  sounds,  197 
WEDEMEYER,     mechanics    of    thoracic 

movements,  429 

WEIDENREICH,  haemolymphatic  glands, 
557 

red  blood-corpuscles,  121 
WEIGERT,  fats  in  blood,  127 
WEISS,  lymph,  516 
WEISSMANX,  heredity,  49,  62 
WELCKER,  haemocytometry,  102 

quantity  of  blood,  99,  121 
WELDON,  origin  of  species,  63 
WELLS,  H.  G.,  autolysis,  40 
WENCKEBACH,  venous  pulse,  203 
WERTHEIMEU,  respiratory  centres,  448, 

451 

WHEATSTONE,  bridge  of,  150 
WILLCOCK,  E.  G.,  amino-acids,  40 
WILLIAMS,  heart  sounds,  197 
WILLIAMS,  cardiac  vagus,  218 

tonographic  apparatus,  288 
WILLIS,  R.,  circulation  of  blood,  179 
WINOGRADSKY,  nitrification  by  bacteria, 

58 

WINSLOW,   auriculo-ventricular  valves, 
192 

intercostal  muscles,  411 
WINTER,    erythrocytes,    isotonic    solu- 
tion, 106 

molecular  concentration  of  blood,  143, 

155 

WINTERSTEIN,      nerve      centres      and 
oxygen,  394 

heart  oxygen,  294,  338 

true  apnoea,  491 
WINTRICH,  heart  sounds,  197 
WOLFFBERG,  pulmonary  catheter,  388 
WOLLASTON,  muscle  sound,  197 
WOODWORTH,    R.    S.,    contraction    of 

heart,  338 

WOOLDRIDGE,  depressor,  334 
WoRM-MuLLER,   transfusion   of   blood, 

152 

WRIGHT,  A.  E.,  bactericidal  power  of 
blood,  156 

coagulation  of  blood,  140,  156 

YEO,  oxygen  and  heart,  293 


592 


PHYSIOLOGY 


YERKES,  R.  M.,  entomostraca  and  light, 
90 

ZACCAIIELLI,  splenectomy,  555 

ZANETTI,  seromucoids,  126,  129 

V.   ZIEMSSEX,  afferent  fibres   of  heart, 

.   335 
ZUNTZ,  aeapnia,  475,  504 


ZUNTZ,  blood  gases,  380,  386,  400 

dyspnoea,  470 

foetal  blood,  477 

periodic  respiration,  501,  504 

pulmonary  gas  exchange,  392,  400 

reaction  of  blood,  96 

work  of  heart,  230 
ZWEIFEL,  foetal  blood,  477 


END    OF   VOL.    I 


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